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SCHOOL   OF   MEDICINE 


ARTERIOSCLEROSIS 

DISEASES   OF  THE   MEDIA 


By  OSKAR   KLOTZ 


ISitUtmti^  Htbrarg 


PUBLICATIONS  FROM  THE 
UNIVERSITY  OF  PITTSBURGH  MEDICAL  SCHOOL 

PATHOLOGICAL  LABORATORIES 


ARTERIOSCLEROSIS 

DISEASES  OF  THE  MEDIA 
AND  THEIR  RELATION  TO  ANEURYSM 


BY 


OSKAR  KLOTZ,  M.B.  (tor.),  M.D.C.M.  (mcgill) 

Professor  of  Pathology  and  Bacteriology,  University  of  Pittsburgh,  Pittsburgh,  Pa.; 

Late  Lecturer  in  Pathology,  McGill  University,  Montreal ;  and  Assistant 

Pathologist  Royal  Victoria  Hospital,  Montreal 


Press  of 

The  new  Era  Printing  Company 

Lancaster.  Pa. 

January,  1911 


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L, 


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K  69 


APR  l3t9H 


PREFACE. 

I  make  no  apology  for  adding  to  an  already  enormous  literature 
on  Arteriosclerosis,  but  I  ask  the  readers'  indulgence  for  a  possible 
criticism  on  the  brevity  of  many  discussions.  The  various  processes 
which  concern  arteriosclerosis  merit  chapters  for  each,  but  the  pres- 
ent undertaking  was  not  intended  to  assume  such  pretentious  pro- 
portions. As  it  is,  the  discussion  has  grown  beyond  our  expec- 
tations. 

The  bringing  together  of  the  observations  and  facts  concerning 
the  processes  of  disease  which  affect  the  middle  coats  of  the  arteries 
is  to  emphasize  the  importance  and  frequency  of  these  conditions. 
For  some  years  attention  has  repeatedly  been  directed  (Virchow 
1856,  Thoma  1883,  Jores  1903)  to  the  disease  of  the  intima,  with 
but  casual  reference  to  the  medial  scleroses.  Heller,  Chiari  and 
others  have  demonstrated  the  importance  of  syphilitic  mesaortitis, 
Moenckeberg  has  pointed  out  the  frequency  of  medial  sclerosis,  but 
much  can  not  be  obtained  in  the  literature  concerning  medial  arterio- 
sclerosis as  a  group  disease. 

Particularly  to  the  clinician  has  the  subject  of  arteriosclerosis 
been  a  difficult  one, — and  at  the  same  time  the  most  interesting. 
The  protean  manifestations  of  the  disease  are  such  that  some  type 
of  it  is  to  be  observed  by  every  practitioner  and  specialist.  What 
has  been  its  origin,  what  are  to  be  the  results,  are  questions  which 
must  be  answered  separately  in  each  case. 

It  is  hoped,  that  in  putting  together  our  own  findings  with  those 
of  others,  we  have  at  least  to  some  degree,  cleared  this  difficult 
subject  of  some  of  its  underbrush  and  allowed  the  more  important 
facts  to  present  themselves. 

This  work  was  started  in  1905  and  was  nearing  completion  when 
the  author,  in  the  disastrous  fire  at  McGill  University  in  1907,  lost 
the  entire  materials,  manuscript  and  drawings.  To  repeat  the  work, 
recollect  the  literature,  microscopic  sections  and  drawings  was  dis- 
heartening and,  I  would  almost  say,  uninteresting.     The  greater 

iii 


iv  Preface. 

part  of  the  practical  work  was  undertaken  while  the  author  was 
associated  with  the  Pathological  Laboratory  of  the  Royal  Victoria 
Hospital  at  Montreal. 

I  am  very  much  indebted  to  my  former  chief,  Professor  J.  G. 
Adami,  for  his  criticisms  and  suggestions  on  this  paper.  Although, 
in  respect  to  the  nature  and  cause  of  intimal  scleroses,  our  views  do 
not  entirely  coincide,  a  lengthy  discussion  on  this  topic  has  been 
omitted  as  not  bearing  directly  on  my  subject.  For  the  fuller  treat- 
ment of  intimal  arteriosclerosis,  I  refer  the  reader  to  our  respective 
articles  in  the  American  Journal  of  Medical  Sciences,  1909,  and  in 
the  Journal  of  Experimental  Medicine,  1910. 

O.K. 
Pittsburgh,  Pa. 


CONTENTS. 

Introduction    i 

Normal  Histology  of  Arteries 5 

(a)  Arteries  of  the  elastic  type  7 

(b)  Arteries  of  the  muscular  type 11 

Functions  of  the  Media  14 

Diseases  Affecting  the  Media  16 

Productive   Changes    18 

(a)   Hypertrophy  of  the  Media  19 

(&)  Acute  Mesarteritis    22 

(c)  Chronic  Mesarteritis    27 

(d)  Periarteritis   Nodosa    36 

Degenerative  changes 40 

(a)  Atrophy    40 

(b)  Necrosis    44 

(c)  Fatty  Degeneration 45 

(d)  Calcareous  Degeneration   51 

(e)  Bone  and  Cartilage  in  the  Media  57 

(/)   Hyaline  and  Amyloid  Degeneration  59 

Experimental  Medial  Diseases  of  the  Arteries 63 

Productive  changes  64 

Degenerative  changes  -. 65 

Etiological  Factors  of  Medial  Diseases  70 

(a)  Infections    71 

(b)  Poisons  and  Toxins  73 

(c)  Work   74 

(d)  Old  Age  76 

Aneurysms  and  Medial  Disease  79 

Summary    100 

Bibliography  103 


Arteriosclerosis.     Diseases  of  the  Media. 

By  OSKAR  KLOTZ. 


introduction. 

Our  knowledge  concerning  the  etiology  of  arteriosclerosis  has 
been  much  enhanced  by  the  experimental  work  done  on  this  subject, 
and,  with  the  information  thus  acquired,  our  views  respecting  this 
disease  have  changed  to  a  considerable  extent.  It  is  now  realized 
that  the  disease,  instead  of  being  generalized  and  affecting  the  entire 
arterial  tree,  (i)  may  be  localized,  affecting  the  arteries  of  one 
particular  organ,  (2)  may  involve  one  particular  type  of  artery 
only,  and  (3)  may  be  limited  to  one  or  other  zone  of  the  arterial 
coat.  Not  infrequently  at  the  post-mortem  table  we  are  impressed 
by  the  extensive  sclerosis  of  the  arteries  of  the  brain,  and  the  coinci- 
dent absence  of  anything  approaching  to  marked  involvement  of  the 
rest  of  the  arterial  system.  Nor  is  it  possible  for  any  one  to  make 
more  detailed  investigations  of  the  arteries  of  case  after  case,  such 
as  those  which  have  formed  the  basis  of  this  article,  without  becom- 
ing convinced  at  an  early  stage  that  the  extent  of  the  disease  mani- 
fested in  the  aorta  bears  no  relationship  to  that  found  in  the  peri- 
pheral vessels. 

With  all  the  advances  that  have  been  made,  there  still  remains 
not  a  little  uncertainty  as  to  how  best  to  classify,  that  is,  to  coordi- 
nate and  bring  into  relationship  the  many  conditions  affecting  the 
arterial  wall,  differentiated  during  the  last  generation,  and  included 
under  the  general  headings  of  scleroses  and  atheroma.  Regarding 
the  intimal  changes,  it  may  be  said  that  the  more  recent  studies  of 
Jores  and  others  have  established  a  satisfactory  basis  for  such  classi- 
fication. The  same  cannot  be  said  regarding  the  changes  in  the 
media.  There  is  still  much  confusion,  both  as  to  the  nature  and 
mode  of  development  of  these  changes,  and  as  to  the  relationship 
between  medial  and  intimal  disturbances.  It  has  seemed  to  me 
timely  to  make  a  careful  study  of  the  conditions  affecting  the  media, 

1 


2  Arteriosclerosis.    Diseases  of  the  Media. 

in  the  hope  that  thereby  coordinating  my  own  observations  with 
those  of  previous  workers,  light  may  be  thrown  upon  the  subject. 
The  present  study,  therefore,  is  devoted  to  a  detailed  consideration 
of  certain  disturbances  affecting  the  media. 

At  the  very  onset  we  encounter  the  difficulty  of  nomenclature. 
What  general  term  is  to  be  employed  to  embrace  the  group  of  mor- 
bid states  included  in  this  study  ?  Some,  like  Jores,  are  inclined  to 
lay  down  that  arteriosclerosis  is  essentially  an  intimal  disease,  and 
one  particular  order  of  intimal  affections  at  that :  morbid  states  of 
the  media  cannot,  they  hold,  be  included  under  this  term.  This  I 
cannot  but  think  is  too  narrow  a  view.  In  employing  any  medical 
term,  we  are  bound,  when  possible,  to  keep  in  mind  its  root  meaning, 
and  the  significance  afforded  to  it  by  its  author.  Now  "arterio- 
sclerosis "  is  literally  the  state  of  hardness  of  the  arteries,  and  Lob- 
stein,  who  introduced  the  term,  employed  it  to  cover  all  conditions 
in  which  the  arteries  were  noticeably  hardened  to  the  touch  upon 
clinical  examination.  Here,  I  would  repeat  what  I  have  noted  else- 
where, that  the  hardening  of  the  radials  which  affords  a  common 
clinical  diagnosis  of  arteriosclerosis  is  due  in  general  to  medial  and 
not  intimal  change.  I  have  thus  no  hesitation  in  including  the 
medial  conditions  here  under  review,  under  the  heading  of  arterio- 
sclerosis. 

Marchand's  recent  interpretation  of  arteriosclerosis,  "that  in 
general  we  must  include  those  changes  in  the  arteries  which  lead  to 
a  thickening  of  the  wall,  and  more  particularly  of  the  intima,  in 
which  not  only  degenerative  changes  (fatty  with  its  sequelae), 
sclerosis  and  calcification  (including  calcification  of  the  media) 
arise,  but  also  inflammatory  and  productive  processes,"  is  very  com- 
plete. From  this  definition  there  remains  no  doubt  that  all  types  of 
changes  in- any  of  the  three  coats  of  an  artery,  which  have  as  a  con- 
sequence a  thickening  or  hardening  of  the  wall,  are  of  an  arterio- 
sclerotic nature;  and  let  us  repeat  too,  that  those  changes  may  be 
either  degenerative  or  productive  in  kind.  It  will  be  appreciated 
that,  on  taking  this  view,  the  common  type  of  calcification  of  the 
media  as  it  is  found  in  the  peripheral  vessels  is  also  an  arterio- 
sclerosis.    Savill  also  employs  the  term  arteriosclerosis  in  the  gen- 


Introduction.  3 

eral  sense,  and  classifies  the  disease  into  three  types,  the  intimal, 
medial  and  adventitial. 

Let  us  freely  admit  that,  employed  thus,  the  term  arteriosclerosis 
becomes  generic  and  not  specific,  that  several  types  of  arteriosclerosis 
must  be  recognized,  and  so  as  each  type  is  worked  out  and  its 
characters  definitely  known,  either  a  qualifying  adjective  must  be 
employed  to  indicate  that  type,  or  a  special  name  be  given  it. 
Already  there  is  a  definite  movement  in  this  direction.  Thus 
through  the  work  of  Heller,  Doehle  and  Chiari,  the  existence  of  a 
distinct  and  typical  specific  inflammatory  affection  of  the  media  has 
become  recognized,  syphilitic  mesarteritis  (mesaortitis  productiva 
syphilitica),  while  in  order  to  abolish  the  confusion  in  the  employ- 
ment of  terms  between  intimal  sclerosis  and  its  later  stage  of 
atheroma,  Marchand  has  launched  the  term  atherosclerosis  or 
atherosis,  and  this  has  been  hailed  with  avidity  by  several  leadirig 
workers  in  Germany.  For  myself,  I  welcome  either  of  these  latter 
words  as  affording  a  useful  designation  for  the  common  type  of 
intimal  arteriosclerosis,  and  helping  to  differentiate  this  form  from 
medial  arteriosclerosis  in  which  characteristically  there  is  not  en- 
countered atheroma  proper.  In  dealing  thus  with  the  different 
types  of  medial  arteriosclerosis,  I  shall  not  follow  the  time-honored 
custom  of  leading  up  to  my  subject  by  means  of  an  historical  intro- 
duction. To  do  this,  to  recount  conscientiously  the  successive  obser- 
vations that  have  been  made  upon  the  part  played  by  the  media  in 
the  development  of  arteriosclerosis,  in  an  era  when  this  was  re- 
garded as  a  single  disease,  and  to  appraise  those  observations  at 
their  right  value  would  introduce  prematurely,  material  which  must 
of  necessity  be  repeated  later  in  the  orderly  study  of  the  different 
types  of  medial  arteriosclerosis. 

It  would  be  better  to  refer  to  these  early  observations  in  a  syste- 
matic description  of  those  types  of  disease.  Here,  at  most,  it  is 
fitting  that  four  names  be  recalled:  that  of  Johnson,  who  first 
recognized  the  existence  of  hypertrophy  of  the  media,  and  more 
particularly  of  the  muscular  constituents  of  the  small  arteries ;  of 
Thoma,  who  laid  stress  upon  degeneration  and  weakening  of  the 
media  of  the  aorta  and  larger  arteries,  as  favoring  subsequent 
intimal  sclerosis;  of  Francis  Welch,  who  first  described  clearly  the 


4  Arteriosclerosis.    Diseases  of  the  3Iedia. 

syphilitic  inflammatory  type  of  medial  disease ;  and  of  Moenckeberg, 
who  made  the  first  serious  study  of  medial  degeneration  as  a 
separate  entity. 

A  much  more  satisfactory  introduction  to  our  subject  will  be 
from  the  standpoint  of  arterial  structure.  It  is  becoming  increas- 
ingly recognized  that  the  different  parts  of  the  arterial  system  differ 
widely  in  their  histological  constitution,  in  that  the  structure  of  any 
given  artery  is  intimately  associated  with  its  function — structure 
and  function  in  fact  being  largely  interdependent.  From  this,  it 
follows,  (i)  that  the  same  noxa  acting  upon  arteries  of  different 
types  will  have  different  effects  and  (2)  that  anything  of  the  nature 
of  an  adequate  knowledge  of  disease  of  the  arteries — in  this  case  of 
medial  disease — must  be  preceded  by  the  knowledge  of  the  normal 
histology  of  the  different  types  of  the  arteries.  What  otherwise 
would  seem  to  be  wholly  dissimilar  lesions,  may  be  the  expression  of 
the  action  of  a  common  factor ;  nay,  taking  a  yet  broader  outlook, 
and  regarding  not  one  coat  of  the  artery  alone,  but  the  whole  artery ; 
with  these  pronounced  differences  in  structure,  it  may  be  that  of 
functional  structure,  exercises  a  decided  influence  in  the  course  of 
the  disease  and  the  nature  of  the  lesions  there  attained. 

In  making  the  last  suggestion,  I  am  passing  beyond  the  limits  here 
set.  It  is  sufficient  to  lay  down  that  a  knowledge  of  the  structure  of 
the  media  in  various  parts  of  the  arterial  tree  must  precede  any 
satisfactory  discussion  of  medial  disease. 

As  has  been  pointed  out  recently,  the  type  of  arterial  change 
(pathological),  as  well  as  its  extent,  depends  upon  two  factors — (i) 
the  work  and  function  of  the  tissue  supplied,  and  (2)  the  histo- 
logical structure  of  the  vessel :  we  will  be  obliged  to  discuss  these 
details  at  length.  We  will  also  show  in  how  far  the  vessels  in 
different  organs  differ  in  their  histological  structure.  This,  I  have 
found,  influences  the  nature  of  the  disease,  which  may  arise  in  the 
vessel.  We  are  becoming  familiar,  and  this  mainly  through  the 
work  on  experimental  animals,  with  the  action  of  different  drugs 
and  poisons  on  the  vascular  tissues.  That  certain  poisons  and 
toxins  have  definitely  a  selective  action  for  certain  tissues  is  well 
known,  and  this  point  too  is  being  demonstrated  in  the  effect  of 
poisons  on  the  arterial  wall. 


HISTOLOGY. 

Anatomically,  the  arteries  are  divided  into  three  types,  the  large, 
the  medium  sized,  and  the  small  vessels.  Under  the  large  sized 
vessels  are  included  the  aorta  and  its  main  branches  in  the  neck  and 
abdomen.  The  medium  sized  vessels  are  the  secondary  and  tertiary 
branches,  arising  from  the  first  type,  while  the  small  arteries  include 
all  the  peripheral  arteries  down  to  the  finest  divisions  into  capillaries. 
This  classification  of  the  arteries  is  an  entirely  arbitrary  one,  with- 
out any  proper  delineations  of  each  particular  type,  and  forms  an 
impossible  classification  in  studying  the  finer  structure  of  vessels. 

On  the  other  hand,  the  arteries  have  been  classified  according  to 
their  histological  structure,  and  mainly  on  the  nature  of  the  media. 
The  naked  eye  appearances  of  the  arteries  give  no  clue  to  the  types 
belonging  to  the  histological  classes.  We  are  bound,  therefore,  to 
study  the  structure  of  the  arteries  under  the  microscope,  and  to 
determine  the  structure  of  each  artery,  and  to  place  it  in  its  proper 
class. 

In  the  main,  there  are  histologically  two  types  of  arteries,  ( i ) 
the  elastic  type,  those  in  which  the  elastic  tissue  is  in  equal  or  greater 
proportion  to  the  muscular  tissue  in,  the  media,  and  (2)  the  mus- 
cular type  in  which  the  muscle  elements  are  in  much  greater  propor- 
tion than  the  elastic  fibres  in  the  media.  With  these  subdivisions, 
the  anatomical  classification  is  of  no  service.  The  vessels  which  are 
included  in  the  latter  classification  under  the  large  sized  vessels  do 
not  necessarily  belong  to  a  distinct  histological  class,  and  the  same 
is  true  with  the  medium  and  small  sized  arteries. 

On  the  histological  picture  of  the  arteries  we,  therefore,  base  the 
division  of  our  arteries,  and,  although  certain  vessels  belonging  to 
one  or  other  of  these  types  vary  slightly  in  their  characters  from 
the  main  type,  these  form  only  subdivisions  under  the  main  head- 
ings. I  hardly  think  it  is  necessary  to  designate  these  small  differ- 
ences in  vessels  of  certain  organs  by  separate  names,  since  the  char- 
acters are  isolated  to  the  arteries  of  the  particular  organ. 

Every  artery  is  possessed  of  three  tunics,  the  intima,  media  and 

5 


6  Arteriosclerosis.    Diseases  of  the  Media. 

adventitia :  the  intima  consists  of  an  endothelial  layer,  with  or  with- 
out connective  or  muscular  tissue  layers  between  it  and  the  internal 
elastic  lamina.  The  endothelial  layer,  which  lines  the  lumen  of  the 
artery  is  composed  of  large  flat  cells,  arranged  in  a  mosaic  or  pave- 
ment fashion.  Under  normal  conditions  this  layer  is  but  a  single 
stratum,  which  under  pathological  conditions  becomes  heaped  up  on 
itself  to  form  a  many-layered  tunic.  That  the  cells  forming  the 
pearly  nodules  on  the  endothelium  of  the  blood  vessels  are,  in  part 
at  least,  endothelial  cells,  I  am  fully  convinced,  but  the  discussion  of 
this  question  in  this  paper  would  lead  us  too  far  afield. 

Beneath  the  endothelial  cells  of  the  intima,  there  is  always,  save 
in  the  minutest  arteries,  a  thin  strand  of  connective  tissue  upon 
which  the  endothelial  cells  rest.  In  the  larger  vessels  the  quantity 
of  connective  tissue  present  increases  with  advancing  years  until 
the  age  of  twenty-five  or  thirty  is  reached.  In  the  newborn  the 
quantity  of  connective  tissue  in  the  intima  of  the  aorta  is  hardly 
perceptible,  but,  as  Thoma  and  his  pupils  have  demonstrated,  there 
is  a  constant  production  of  fresh  tissue  of  this  nature,  with  an 
increase  in  the  thickness  of  the  layer  until  adolescence.  From  this 
time  onwards;  the  physiological  quantity  of  connective  tissue  in  the 
intima  remains  fairly  constant,  and  any  increase  must  be  looked  on 
as  pathological. 

Of  the  muscular  elements  in  the  intima  little  need  be  said  at  this 
juncture,  though  much  importance  is  attached  to  them  in  the  pathol- 
ogy of  intimal  arteriosclerosis.  These  muscle  fibres  are  found  only 
in  the  larger  vessels  and  form  a  layer  lying  next  to  the  inner  side  of 
the  elastic  lamina.  These  muscle  elements  are  of  the  unstriped 
variety  and  have  a  longitudinal  direction  in  the  artery.  I  have 
never  convinced  myself  of  their  uniform  presence  in  the  vessels  of 
the  muscular  type.  Often  this  lamella  is  but  two  or  three  cells  in 
width,  though  at  other  times  this  muscular  layer,  which  is  called  the 
musculo-elastic  layer,  is  of  considerable  thickness,  occupying  as 
much  as  one  third  of  the  thickened  intima.  Among  the  muscle 
fibres  there  is  a  fine  network  of  elastic  fibrils  which  have  a  relation 
to  the  internal  elastic  lamina.  There  seems  to  be  little  significance 
to  be  attached  to  the  fine  elastic  elements  as  they  normally  exist  in 
the  musculo-elastic  layer,  but  with  advancing  age,  and  in  diseased. 


Histology.  7 

particularly  weakened,  states  of  the  artery  these  fibres  become 
increased  in  quantity  and  size,  and  indicate  according  to  their  char- 
acters, certain  sclerotic  changes  in  the  vessel. 

Under  certain  conditions  of  stress  the  musculo-elastic  layer  may 
become  uniformly  hypertrophied,  without,  however,  there  being  any 
diseased  condition  in  it  or  in  any  other  parts  of  the  arterial  coat. 

The  internal  elastic  lamina  is  present  in  arteries  of  all  sizes  and 
structures,  but  differs  in  its  nature  in  the  two  types  of  vessels.  The 
media,  which  is  the  mainstay  of  the  arteries,  and  which  is  the  dis- 
tinguishing point  between  the  smallest  arteries  and  the  capillaries 
arising  therefrom,  is  also  to  be  found  in  all  arteries.  This  tunic 
consists  in  every  case  of  unstriped  muscle  tissue  along  with,  in  some 
cases,  more  or  less  elastic  fibres,  and  to  a  slight  extent,  connective 
tissue.  The  media  is  bounded  on  its  outer  side  by  an  external 
elastic  lamina,  which  also  varies  in  the  different  types  of  arteries. 
The  adventitia  forming  the  outermost  tunic,  is  made  up  of  varying 
amount  of  connective,  elastic  and  musclar  tissue.  Each  of  these 
elements  fluctuates  in  quantity  to  a  very  great  extent  in  the  arteries 
of  the  different  organs. 

Arteries  of  the  Elastic  Type. — The  arteries  belonging  to  this 
class  are  the  aorta,  the  first  portions  of  its  main  branches  at  the 
arch,  the  first  part  of  the  common  iliacs  and  the  pulmonary. 
As  our  interest  is  mainly  centered  upon  the  structure  of  the 
media,  I  shall  dispense  with  the  discussion  of  the  minute  histology 
of  the  intima.  Suffice  it  to  say  that  the  intima  in  the  arteries 
of  the  elastic  tissue  type  is  of  far  greater  importance  than  in 
those  of  the  muscular  type.  And  further  the  structure  of  the 
intima  in  the  former  is  the  more  complex,  and  embraces  more  tissue 
elements  than  is  found  in  the  latter.  The  endothelial  lining  which 
is  common  to  all  vessels  occupies  the  innermost  layer  and  lies  upon 
a  slight  amount  of  supporting  connective  tissue,  followed  then  by  a 
layer  of  longitudinally  placed  muscle  fibres,  as  has  been  described 
above.  These  muscles  fibres  are  separated  from  the  media  by  the 
internal  elastic  lamina,  which  is  usually  considered  a  part  of  the 
intima. 

However,  it  is  not  accepted  by  all  that-  the  internal  fenestrated 
membrane  belongs  to  the  intima.     Bonders  and  Jansen  express  the 


8  Arteriosclerosis.     Diseases  of  the  Media. 

opinion  that  all  parts  of  the  vessel  wall  containing  muscle  elements 
belong  to  media,  and  v.  Ebner  points  out  that  there  is  no  sharp 
division  between  the  intima  and  media.  He  is,  therefore,  inclined 
to  side  Avith  the  histological  subdivisions  given  by  Bonders  and 
Jansen. 

It  is  evident  that  this  view  is  incorrect  as  has  been  pointed  out  by 
Westphalen  and  Remak.  The  coats  of  the  arteries  are  to  be  dis- 
tinguished rather  by  the  direction  of  the  fibres  than  by  the  actual 
elements  they  contain. 

This  internal  elastic  lamina,  which  bounds  the  inner  side  of  the 
media  in  all  arteries,  exists  in  varying  quantities,  and  is  often  diffi- 
cult to  distinguish  from  the  other  elastic  lamina  present  in  the 
media.  In  vessels  of  the  elastic  type,  the  internal  elastic  lamina  is 
but  the  innermost  of  many  lamellse,  which  are  present  in  the  media. 
In  young  individuals  this  innermost  lamella  presents  no  difference 
from  the  ordinary  elastic  rings  in  the  media  and  lies  close  under- 
neath the  endothelium,  with  but  a  few  connective  tissue  cells 
between  it  and  the  endothelial  layer  of  the  intima.  In  adults,  how- 
ever, where  the  intima  has  gained  in  thickness,  the  internal  elastic 
lamella,  too,  becomes  more  prominent  and  presents  a  definite 
boundary  zone  between  it  and  the  media.  This  increase — it  may 
be  the  groAvth  of  the  elastic  tissue  in  general — can  be  obserA-ed  with 
increasing  age. 

In  a  child  up  to  three  years  the  internal  elastic  lamina  of  the 
arteries  of  the  elastic  type  presents  a  narrow  band-like  appearance, 
identical  with  its  neighboring  bands  in  the  media.  Its  characters 
are  the  same,  and  it  is  of  the  same  size  as  those  in  this  tunic.  At 
this  age  it  is  to  be  noted  that  the  elastic  bands  show  no  branching 
or  splitting  of  their  substance.  This  branching  does,  however, 
occur  as  age  advances.  At  the  age  of  twenty,  the  elastic  strands 
have  become  perceptibly  thicker  and  have  sent  out  a  large  number 
of  thread-like  elastic  elements  into  the  neighboring  muscle  tissue, 
and  this  increase  in  size  and  number  of  elastic  fibres  progresses 
steadily  with  age.  The  process  of  increase  is  not  confined  to  the 
elastic  elements  of  any  one  part  of  the  vessel,  but  can  be  followed  in 
any  one  of  the  tunics. 

I  should  like  to  note  here  that  the  splitting  of  the  internal  elastic 


Histology.  9 

lamina,  upon  which  some  ( Jores)  have  laid  so  much  stress,  as  being 
the  chief  characteristic  of  arteriosclerosis,  is  not  alone  confined  to 
this  lamella,  but  similar  changes  are  to  be  noted  in  the  elastic  fibres 
of  the  media  in  arteriosclerotic  processes  or  in  old  age.  To  this  I 
shall  refer  again. 

To  the  outer  side  of  the  internal  elastic  lamina  lies  the  media,  a 
definite  structure,  well  defined  on  both  its  inner  and  outer  borders. 
As  the  internal  elastic  lamina  bounds  the  media  on  its  inner  side,  so 
the  external  elastic  lamina  or  Henle's  membrane  forms  its  outer 
boundary.  There  is  this  difference,  however,  that  whereas  the 
intimal  elastic  lamina  is  normally  made  up  of  a  single  strand,  the 
external  lamina  may  be  composed  of  one  or  more  elastic  bands,  all 
of  which  do  not  run  in  the  same  direction.  In  the  vessels  of  the 
elastic  tissue  variety  it  is  difficult  to  denote  any  particular  strand  of 
elastic  tissue  as  the  external  limiting  membrane,  save  that  the  first 
elastic  layer  lying  beyond  the  outermost  of  the  circularly  disposed 
muscular  fibres  is  to  be  considered  the  membrane  in  question,  or  in 
other  words,  the  external  elastic  lamina  is  the  last  of  the  concentric 
bands  of  the  media.  On  its  outer  side,  the  lamella  usually  shows  a 
number  of  offshoots  which  go  to  make  up  the  scattered  elastic  fibres 
of  the  adventitia.  The  external  lamina  is  seldom  more  prominently 
defined  than  any  of  the  other  elastic  bands  of  the  media;  and  hence 
can  scarcely  be  looked  on  as  an  individual  structure. 

The  media  of  these  vessels  shows  the  characteristic  alternating 
layers  of  elastic  fibres  and  muscle  bundles.  These  elastic  fibres 
differ  in  no  way  from  the  internal  elastic  lamina  of  these  vessels, 
save  that  whereas  the  internal  elastic  lamina  normally  sends  off  few 
if  any  ramifications,  the  elastic  elements  in  the  media,  although 
concentrically  arranged  give  off  connecting  bridges  of  elastic  tissue 
which  weld  the  tunic  into  a  more  compact  structure.  There  are 
usually  from  forty  to  sixty  of  these  elastic  rings  separated  by 
intervals  of  lo  to  20  microns. 

We  have  now  come  to  recognize  the  importance  of  the  elastic 
elements  in  the  structure  of  the  arteries.  In  them,  we  find  that  the 
nature  and  disposition  of  the  elastic  fibres  varies  with  the  changing 
function  of  the  vessels.  In  the  main  it  might  be  said  that  where 
strength  and  resistance  are  required  in  the  circulatory  system,  there 


10  Arteriosclerosis.    Diseases  of  the  Media.    . 

is  the  need  of  elastic  elements.  This  is  not  only  true  in  normal 
vessels  but  also  in  pathological  states.  Thus  the  large  arteries 
which  receive  the  direct  stress  of  the  heart  beat  are  well  provided 
with  elastic  fibres,  while  the  muscle  tissue  of  less  importance  for  the 
maintenance  of  elasticity  occupies  a  less  prominent  position  and  is 
less  in  quantity. 

I  would  here  point  out  that  the  conversion  of  the  intermittent 
blood  flow  from  the  heart  into  a  more  constant  stream,  is  a  work 
resting  to  a  great  extent  upon  the  elastic  fibres.  In  these,  nature 
has  provided  a  tissue  which  evinces  no  signs  of  fatigue,  and  which 
is  able  to  take  on  a  considerable  reserve  work,  accommodating  itself 
eventually  by  a  hyperplasia  of  its  own  elements.  I  would  point  out 
too  that  the  reverse  is  the  case  with  the  much  overworked  muscle 
tissue.  The  latter  is  subject  to  fatigue,  like  voluntary  muscle  fibres, 
and  in  this  stage  of  fatigue  no  hyperplasia  takes  place,  but  in  its 
place  degenerative  processes  occur,  which  as  I  shall  refer  to  later,  is 
of  great  significance  in  the  medial  disease  of  the  arteries  of  the 
lower  extremities. 

The  same  observations,  which  were  made  concerning  the  develop- 
mental change  in  the  internal  elastic  lamina,  are  applicable  to  the 
elastic  rings  of  the  media.  In  fact,  it  is  to  be  understood  that  each 
one  of  these  rings  differs  in  no  essential  way  from  the  internal 
lamina.  Thus  we  are  to  picture  the  general  structure  of  the  elastic 
stroma  as  a  system  of  tubes  which  fit  into  each  other,  and  leaving 
an  appreciable  space  between  the  contiguous  tubes.  Another  feature 
common  to  all  these  elastic  tubes  is  that  they  have  certain  fenestra- 
tions which  allow  communication  between  the  spaces  occupied  by 
the  muscle  elements  and,  further,  allow  the  passage  of  the  vasa 
vasorum. 

Whereas,  the  elastic  fibres  in  young  individuals  up  to  the  age  of 
twelve,  are  arranged  in  concentric  layers  and  in  life  form  concentric 
cylinders  about  the  vessel,  with  few  or  no  elastic  fibrils  between  the 
rings,  there  is  with  the  later  development  of  the  vessels  the  appear- 
ance of  new  fibres  which  link  the  elastic  rings  together  and  form  a 
network  among  the  muscle  bundles.  The  comparison  of  an  infant's 
aorta  and  that  of  an  adult  illustrates  this  variation  in  the  elastic 
fibres  very  well.     Particularly  in  old  age — even  when  all  evidence 


Histology.  11 

of  an  arteriosclerotic  process  is  wanting — the  relative  increase  in 
the  elastic  tissue  is  evident.  Not  only  do  new  fibres  appear  between 
the  concentric  rings,  but  the  original  elastic  strands  become  thick- 
ened and  heavier.  These  changes  in  old  age  occur  at  the  expense 
of  the  muscle  tissue  which  is  relatively  decreased  and  more  closely 
crow^ded  together. 

The  muscle  fibres  of  the  media,  which  lie  between  the  concentric 
elastic  elements  are  entirely  of  the  unstriped  variety,  and  these  alone 
endow  the  artery  with  active  contractile  powers.  The  greater 
majority  of  these  muscle  fibres  are  circularly  disposed,  while  a  few 
fibres  hold  an  aberrant  radial  position  or  stretch  lengthwise  with  the 
artery.  There  is  but  very  little  connective  tissue  about  the  muscle 
bundles,  but  there  is  a  fair  amount  along  the  course  of  the  vasa 
vasorum  which  penetrate  the  media  from  the  adventitia  to  its  outer 
third.  The  individual  fibres  are  spindle  shaped,  and  are  about  40  to 
60  microns  long. 

While  the  elastic  fibres  are  capable  of  being  stretched  and  then 
of  returning  to  their  former  length,  they  are  incapable  of  contract- 
ing beyond  this  given  length.  Naturally,  therefore,  these  vessels, 
of  the  elastic  type,  which  possess  only  a  partial  muscular  media, 
cannot  undergo  the  wide  variations  in  the  size  of  their  lumina,  being 
prevented  from  undue  dilatation  by  the  strength  of  the  elastic  fibres, 
and  hindered  from  extensive  contraction  by  the  want  of  sufficient 
muscular  elements  and  by  the  impediment  offered  by  the  fully  con- 
tracted elastic  bands.  This  presents  the  main  difference  of  function 
between  the  vessels  of  the  elastic  type  and  those  of  the  muscular 
type. 

Arteries  of  the  Muscular  Type. — The  arteries  of  the  muscular 
type  include  all  the  medium  sized  vessels  mentioned  above  and  the 
large  group  of  "peripheral  arteries."  The  main  characteristic  of 
these  vessels  is  the  large  amount  of  muscle  tissue  in  the  media,  with 
but  few  elastic  fibres  coursing  through  this  tunic.  Although  these 
vessels  are  more  or  less  deficient  in  elastic  fibres  in  the  muscularis, 
they  have  a  well  marked  internal  elastic  band  consisting  of  a  single 
strand,  which  after  death  is  so  commonly  found  to  lie  in  smooth 
folds. 

During  life  this  internal  lamella  is  stretched,  by  the  blood  pres- 


12  Arteriosclerosis.    Diseases  of  the  Media. 

sure,  into  a  smooth  band — or  strictly,  a  perfect  cylinder,  though  no 
doubt  between  each  pulsation  it  is  thrown  into  wavy  folds  becoming 
a  corrugated  cylinder,  by  the  muscular  contraction  of  the  media. 
That  the  internal  elastic  lamina  during  life  lies  in  a  smooth  band 
can  be  demonstrated  by  filling  a  vessel  with  melted  paraffin  under  a 
pressure  equal  to  normal  blood  pressure,  and  then  allowing  the 
paraffin  to  set  while  the  vessel  is  hardened.  The  even  contour  of 
the  internal  elastic  band  is  also  noted  in  cases  of  calcification  of  it, 
when  it  is  found  that  this  lamina  lies  as  a  circular  lamella,  inter- 
rupted only  at  those  points  where  the  muscular  contraction  has 
ruptured  the  calcified  strands.  In  diseased  conditions  of  the  intima 
the  internal  elastic  lamina  may  be  reduplicated  (Jores,  Marchand, 
Aschoff  and  others),  so  that  instead  of  having  only  a  single  layer, 
there  are  now  two  or  more. 

The  media  in  the  vessels  of  the  muscular  type  is  composed,  in  at 
least  nine  tenths  of  its  structure,  of  muscle  fibres.  These  fibres  are 
on  a  whole  of  a  concentric  arrangement,  but,  nevertheless,  have  the 
muscle  tissue  divided  into  bundles  separated  by  thin  layers  of  con- 
nective tissue.  It  is  in  this  connective  tissue  that  the  fine  elastic 
fibrils  appear.  The  few  elastic  fibres  which  are  found  in  the  media 
are  irregularly  disposed,  often  forming  a  fine  arborescent  network, 
but  never  arranged  in  concentric  rings.  The  muscle  bundles, 
although  maintaining  a  general  circular  arrangement  are  frequently 
obliquely  placed,  giving  greater  strength  to  the  wall  of  the  artery. 

The  muscularis  is  bounded  on  its  outer  border  by  an  external 
elastic  lamina,  consisting  of  one  or  more  well  marked  strands. 

This  external  elastic  lamina  is  of  great  importance  as  it  forms  the 
inner  border  of  a  highly  elastic  adventitia.  In  these  vessels  the 
adventitia  contains  relatively  more  elastic  fibres  and  muscle  elements 
than  in  the  arteries  of  the  elastic  tissue  type.  It  must  be  noted  too 
that  the  arteries  of  the  dift'erent  organs  differ  in  the  quantity  of 
elastic  tissue  they  possess  in  the  adventitia.  This  is  well  seen  in 
sections  of  the  spleen  and  of  the  kidney.  In  the  former  the  adven- 
titia is  particularly  rich  in  elastic  tissue,  which  is  true  also  of  the 
arteries  in  the  uterus  while  in  the  kidney  less  of  it  is  present.  The 
external  elastic  lamina  in  these  vessels  is  well  defined  against  the 
muscular  media,  almost  free  from  elastic  fibres. 


Histology.  13 

Normally  while  connective  tissue  elements  do  not  enter  into  the 
structure  of  the  media  of  any  arteries  to  any  great  extent  only  such 
fibres  are  found  which  pass  between  the  muscle  fibres  and  muscle 
bundles  to  weld  a  closer  union  to  the  component  parts.  Besides  this, 
there  is  always  a  small  quantity  of  connective  tissue  along  the  course 
of  the  vasa  vasorum,  which,  except  under  pathological  conditions,  is 
of  no  great  consequence. 

Similar  to  the  arteries  of  the  elastic  type,  the  larger  of  these 
vessels  are  also  provided  with  vasa  vasorum.  Smaller  arteries,  even 
though  provided  with  the  muscular  coat,  do  not  possess  nutritive 
vessels,  save  in  the  outskirts  of  the  adventitia.  In  these  the  thin 
intima  and  the  more  important  media  derive  their  nutrition  from 
the  lumen  of  the  artery  and  from  the  lymph,  which  is  absorbed  from 
the  tissues  surrounding  the  vessel.  In  the  larger  arteries  the  absorp- 
tion of  nutritive  materials  through  the  intima  is  inadequate  for  th« 
demand  of  the  entire  vessel.  In  these  the  vasa  vasorum  penetrate 
from  the  adventitia  into  the  outer  third  of  the  muscularis  and  by 
the  diffusion  of  the  fluids  from  these  vasa  maintain  the  nourishment 
of  both  the  outer  and  middle  third  of  the  media.  It  is  only  under 
pathological  conditions  that  these  vasa  extend  their  branches  beyond 
the  outer  third  of  the  media.  The  inner  third  of  the  muscular  coat 
is  nourished  through  the  intima  from  the  lumen  of  the  artery. 
Possibly  too  this  portion  of  the  vessel  also  obtains  some  nutrition 
from  the  vasa,  but  I  believe  that  the  materials  obtained  from  this 
source  are  small. 

In  evidence  that  the  inner  third  of  the  media  obtains  a  nutritive 
supply  through  the  intima  is  the  fact  that  when  under  diseased  con- 
ditions, the  intima  is  no  longer  able  to  carry  out  its  function  of 
absorption  and  transmission  of  the  fluids  from  the  lumen  of  the 
vessel,  there  occurs  in  the  inner  layer  of  the  media,  as  well  as  in  the 
deep  layer  of  the  intima  a  degeneration  which  is  usually  a  fatty  one. 

It  has  further  been  observed  that  when  an  embolus  or  thrombus 
completely  occludes  the  lumen  of  a  large  artery  while  the  vasa 
vasorum  coming  in  at  the  adventitia  are  undisturbed,  the  portion  of 
the  artery  containing  the  obstructing  mass  shows  degenerative 
changes  in  the  cells  of  the  intima  and  of  the  inner  portion  of  the 
media. 


FUNCTIONS  OF  THE  MEDIA. 

Dependent  upon  the  structure  of  the  media,  the  vessels  of  the 
muscular  type  are  capable  of  extensive  dilatation,  and,  on  the  other 
hand,  of  contraction.  With  a  muscle-power  which  is  able  to  over- 
come the  pressure  within  the  artery  these  vessels  can  readily  modify 
the  quantity  of  blood  passing  through  them. 

This  adaptability  is  essential  to  the  proper  nourishment  of  the 
organs  and  is  well  illustrated  in  the  vessels  of  the  uterus.  During 
menstruation  or  pregnancy  the  uterine  vessels  dilate  to  double  or 
three  times  their  normal  size,  which  size  is  again  assumed  at  the 
end  of  the  process.  This  control  of  the  size  of  the  artery  (lumen) 
is  alone  assumed  by  the  musculature  of  the  media.  Naturally  these 
vessels,  differing  in  their  essential  structure  from  the  arteries  of  the 
elastic  type,  are  subject  to  degenerations  and  diseases  of  quite  a 
different  sort.  The  muscular  vessels  are  a  more  active  type  of 
artery,  and  for  their  nourishment  require  a  greater  number  of  vasa 
vasorum.  These  vasa  do  not  extend  farther  than  through  the  outer 
third  of  the  vessel. 

Goodall  has  recently  pointed  out  that  after  repeated  pregnancies 
the  uterine  artery  is  not  able  to  restore  its  lumen  by  muscular  con- 
traction, and  that  the  diminished  calibre  is  brought  about  by  the 
development  of  new  tissue  within  the  artery.  This  new  inner  tube 
resembles,  in  part,  the  structure  of  the  original  artery. 

Hence  in  considering  the  tissues  composing  the  media  of  the 
different  types  of  arteries,  we  observe  that  the  muscle  cells  are  the 
most  highly  specialized  cells  we  have  to  deal  with  and  they  are  the 
cells  upon  which  the  functions  of  the  arteries  depend.  Whereas 
the  elastic  fibres  form  the  strength  and  resisting  powers  of  the  larger 
arteries,  the  muscle  fibres  are  the  active  working  cells,  which  control 
the  arterial  blood  supply.  Highly  specialized  cells  are  everywhere 
the  cells  which  become  most  easily  damaged  by  various  injuries  and 
noxae,  and  so  we  find  here  also  that  the  muscle  fibres  are  the  most 
prone  to  undergo  degenerative  changes  in  the  media,  and  it  is  only 

14 


Functions  of  the  Media.  15 

in  rare  instances  in  which  we  find  the  other  tissues  (particularly  the 
elastic  fibres)  showing  the  first  degeneration.  The  unstriped  muscle 
fibres  of  the  media  can  show  all  the  degenerative  changes  seen  in 
unstriped  muscle  cells  elsewhere. 

Whatever  function  the  various  component  cells  of  the  media  may 
have,  the  media  as  a  whole  forms  the  mainstay  of  the  artery.  All 
the  variations  in  pressure  brought  about  by  the  heart's  action  act 
upon  and  are  acted  upon  by  the  vessel-walls,  that  is  by  the  media, 
and  it  is  only  through  the  resistance  of  the  latter  that  aneurysms 
do  not  occur  after  great  increase  in  arterial  pressure.  If,  however, 
the  media  is  deseased  and  weakened,  the  vessel  wall  will  not  resist 
normal  blood  pressure,  and  will  develop  in  consequence,  a  localized 
aneurysm  at  the  site  of  weakening. 

The  local  weakening  in  the  wall  of  the  media,  slight  as  this  might 
be,  was  considered  by  Thoma  to  be  always  followed  by  a  little  bulg- 
ing. Relatively  this  is  no  doubt  true,  but  one  must  also  bear  in  mind 
the  earliest  changes  occurring  in  the  media,  and  which  can  be  demon- 
strated in  microscopic  sections,  are  not  of  such  severity  to  cause  a 
giving  way  or  ectasis  of  an  artery.  Such  slight  degenerations  may 
be  fully  mended  without  leading  to  local  or  diffuse  reactions  in  the 
other  coats. 

Broadbent  has  established  the  presence  of  rhythmic  contractions 
in  the  arteries.  These  arterial  pulsations  are  independent  of  the 
heart  beat,  and  have  their  origin  in  the  regular  contractions  of  the 
musculature  of  the  media.  Such  a  system  of  automatic  contractile 
tubes  is  of  importance  in  propelling  the  blood,  particularly  during 
diastole  of  the  ventricle. 


DISEASES  AFFECTING  THE  MEDIA. 

The  diseases  affecting  the  media  of  the  arteries  can  roughly  be 
placed  into  two  groups.  The  one  type,  which  we  will  call  the  pro- 
ductive type  is  characterized  by  the  production  of  new  tissue  cells 
of  whatever  character,  while  the  other  is  essentially  a  degenerative 
one,  with  destruction  of  tissue  as  the  most  marked  feature. 

It  must  be  explained,  however,  that  in  attempting  to  classify  the 
medial  diseases,  it  is  quite  impossible  to  lay  down  fixed  rules  which 
shall  govern  our  grouping.  It  is  so  frequently  the  case  that 
different  types  of  medial  disease  are  present  in  the  same  specimen, 
or  again  that  the  presence  of  one  condition,  such  as  a  degeneration 
in  some  of  the  elements  of  the  media,  has  given  rise  to  other  changes, 
it  may  be  fibrous  proliferation.  It  is  the  unusual  to  find  arterial 
changes  of  but  one  character.  Therefore,  we  must  judge  the  patho- 
logical change  in  a  vessel  by  the  predominant  features  which  are 
present,  but  not  forgetting  that  the  underlying  causes  may  have  been 
of  a  directly  opposite  nature. 

There  is  one  form  of  the  "productive  type"  of  medial  diseases, 
in  which  cellular  proliferation  takes  place  in  the  proportional 
quantities  as  the  tissues  exist  under  normal  circumstances,  which  in 
other  words,  is  a  true  hypertrophy  or  better  hyperplasia.  On  the 
other  hand  the  newly  developed  tissue  may  be  made  up  of  one  or 
other  of  the  elements  in  the  media  in  such  a  proportion  as  to  over- 
shadow the  growth  the  other  cell  elements,  The  tissue,  which  in 
the  vessels  overgrows  the  other  elements,  is,  as  in  other  organs,  con- 
nective tissue  and  represents  (a)  a  chronic  inflammation,  or  (b)  a 
replacement  fibrosis. 

It  becomes  evident  that,  save  for  those  changes  resulting  in  hyper- 
trophy of  the  media,  the  productive  type  is  in  truth  an  inflammatory 
one — using  the  term  in  its  broadest  sense.  The  nature  of  the 
inflammation  and  the  events  leading  to  it,  we  must  discuss  under 
the  various  headings,  into  which  this  class  is  divided. 

By  introducing  the  process  of  inflammation  amidst  the  lesions  of 

16 


Diseases  Affecting  the  Media.  17 

the  media,  and  assuming  a  relationship  of  these  with  arteriosclero- 
sis, will  seem  to  some  a  very  radical  view.  However,  we  must 
assume  sufficiently  broad  principles  to  study  arteriosclerosis  in  all 
the  stages  of  its  development,  and  not  alone  confine  our  attention  to 
the  end  products  of  the  disease.  If  there  is  to  be  any  advance  in 
our  knowledge  of  the  progressive  processes,  and  if  there  is  any  bene- 
fit to  be  obtained  from  these  studies  upon  arterial  diseases  there 
must  be  a  full  understanding  of  the  subject  from  its  beginning. 

No  one  will  to-day  deny  that  inflammation  may  assume  many 
characters  in  different  organs,  and  that  the  vital  reaction  to  irritants 
is  dependent  upon  the  nature  of  the  irritant  and  the  tissue  so 
affected.  That  the  picture  of  an  inflammatory  process  of  one  of  the 
various  coats  of  the  arteries  differs  in  some  respects  from  that  met 
with  elsewhere,  must  be  recognized,  that  however  the  end  result  of 
this  inflammation  is  a  sclerosis,  frequently  due  to  an  overgrowth*  of 
connective  tissue,  must  also  not  be  forgotten. 

It  is  a  question  for  discussion  whether  the  progressive  inflamma- 
tory diseases  in  the  arteries  should  be  taught  under  the  heading  of 
arteriosclerosis,  or  whether  only  the  final  product  of  these  diseases, 
the  sclerosis  or  hardening  of  the  arterial  wall  should  alone  receive 
this  designation.  This  much,  however,  is  certain,  that  he  who 
wishes  to  clearly  appreciate  the  meaning  and  significance  of  arterio- 
sclerosis, must  follow  the  course  of -the  disease  from  its  earliest 
beginning. 

With  this  word  of  explanation,  the  classification  of  the  medial 
diseases  of  the  arteries,  as  given  below,  will  be  better  understood : 

I.  Productive  including  Inflammatory. 

1.  Hypertrophy  of  the  Media. 

2.  Acute  Mesarteritis. 

3.  Chronic  or  Productive  Mesarteritis. 

(a)  Of  Bacterial  Causation. 
Syphilitic.     Chiari's  Type  B. 
Tuberculous. 

Healed  Lesions  of  Other  Infections. 

(b)  Secondary  to  Intimal  Lesions. 
Chiari's  Type  A. 


18  Arteriosclerosis.    Diseases  of  the  Media. 

II.  Degenerative. 

1.  Atrophy  of  the  Media. 

2.  Necrosis  of  Media. 

3.  Fatty  Degeneration  of  the  Media. 

4.  Calcareous  Degeneration. 

(a)   Of  the  Vessels  of  the  Muscular  Type. 
(6)   Of  the  Vessels  of  the  Elastic  Type. 

5.  Hyaline  Degeneration. 

6.  Amyloid  Degeneration. 

In  the  productive  or  inflammatory  type  of  medial  diseases,  the 
process  of  degeneration,  whether  present  or  not,  is  much  less  in 
evidence.  One  must  consider  that  in  all  forms  of  fibroses,  there  is 
a  process  of  degeneration  in  some  one  of  the  tissues,  of  greater  or 
lesser  extent,  accompanying  or  preceding  it. 

Our  second  group  of  medial  diseases  is  one  in  which  the  degen- 
erative processes  come  most  into  prominence.  Under  various  influ- 
ences one  or  other  of  the  tissues  composing  the  media  is  severely 
injured.  At  times  a  single  type  of  tissue  is  injured  consequent  to 
the  selective  action  of  the  noxious  agent.  At  other  times  more 
than  one  tissue  is  injured. 

Directly  dependent  upon  the  amount  and  severity  of  the  degen-. 
erative  processes  there  is  usually  a  certain  regeneration  of  tissue 
amounting  to  repair  and  more  commonly  connective  tissue  forms 
the  bulk  of  the  tissues  entering  into  the  process  of  this  repair.  But 
on  the  whole,  this  regeneration  is  slower  and  does  not  keep  pace 
with  the  amount  of  degeneration  going  on. 

It  is  evident  that  our  classification  is  an  arbitrary  one,  but  one 
which  is  very  obvious  to  the  histologist.  At  times  one  meets  with 
lesions  that  lie  on  the  boundary  line  between  these  two  groups,  and 
in  which  the  amount  of  degeneration  and  regeneration  of  tissue  is 
almost  equal.  These  are  the  rarer  findings  and  do  not  minimize  the 
value  of  classifying  the  medial  diseases  as  we  have  done  above. 

The  classification  as  we  give  it  above  takes  no  cognizance  of  the 
etiological  factors  bringing  about  the  disease  in  question,  because 
it  is  all  but  impossible  to  differentiate  the  forms  of  arteriosclerosis 
by  the  agent  bringing  them  about.     In  the  first  place  we  must 


Diseases  Affecting  the  Media.  19 

recognize  that  the  various  toxic  substances  do  not  affect  all  the 
arteries  in  like  manner,  and  that,  therefore,  a  toxic  arteriosclerosis 
may  refer  to  arterial  lesions  of  different  histological  characters. 
Our  experience  in  experimental  arteriosclerosis  has  also  taught  us 
that  the  same  chemical  agent  can  cause  arterial  lesions  of  different 
kinds,  depending  upon  the  amount  of  the  substance  used. 

Productive  Changes. 

Hypertrophy  of  the  Media. — A  true  hypertrophy  of  the  arteries 
without  other  changes  being  present  is  seldom  met  with,  and  a  uni- 
form hyperplasia  of  the  tissues  is  equally  as  infrequent.  In  1873 
Johnson  noted  an  hypertrophy  of  the  media  in  the  renal  arteries  in 
cases  of  chronic  Bright's  disease,  and  this  was  later  confirmed  by 
Ewald,  von  Leyden  and  Friedemann.  Arteries  showing  similar- 
changes  have  been  noted  by  Westphalen  in  the  uterus.  Marchand 
states  that  such  vessels  in  which  the  media  shows  a  pure  hyper- 
trophy of  the  musculature  without  signs  of  degeneration  should  not 
be  classified  under  arteriosclerosis. 

Jores  noted  that  the  musculo-elastic  layer  of  the  intima  responded 
most  readily  to  hypertrophic  changes,  but  in  most  of  these  cases  the 
hypertrophy  was  soon  followed  by  various  forms  of  degeneration. 
This  we  have  confirmed  for  both  human  arteries  and  those  of 
animals.  Savill  reports  the  common  occurrence  of  hypertrophy  of 
the  media  in  persons  past  middle  life. 

Sternberg,  working  in  Paltauf's  laboratory,  observed  that  in  cases 
of  arteritis  obliterans,  simulating  those  of  Winiwarter  and  Weiss,  a 
hypertrophy  of  the  media  was  present. 

One  finds,  however,  that  other  than  the  isolated  observations  on 
the  renal,  uterine  and  other  vessels,  accurate  reports  are  wanting 
concerning  the  nature  of  the  hypertrophy  in  the  media.  The  infre- 
quency  of  this  lesion  is  due  to  the  fact  that  the  stimuli  leading  to 
hypertrophy  or  hyperplasia  of  the  arterial  tissues  are  seldom  so  well 
graded  that  they  do  not  also  cause  degenerative  changes.  If  it  be 
given  that  the  nourishment  of  these  tissues  is  sufficiently  preserved, 
while  the  stimuli  for  growth,  usually  of  the  nature  of  increased 
work,  are  not  too  severe,  there  is  obtained  uniform  overgrowth  of 
all  the  tissues  in  the  media  as  may  occur  in  other  organs.     Such 


20  Arteriosclerosis.    Diseases  of  the  Media. 

conditions  are  seen  in  the  uterine  vessels  of  young  girls  after  the 
beginning  of  menstruation,  and  in  the  same  vessels  in  young  adults 
after  first  pregnancies.  Here  all  the  factors  for  an  overgrowth  of 
the  arterial  tissues  are  present,  and  in  consequence  a  true  hyper- 
trophy and  hyperplasia  of  the  media  is  the  result.  I  do  not  feel 
convinced  that  such  an  hypertrophy  ever  takes  place  after  the  thirty- 
fifth  year. 

Concerning  hypertrophy  of  the  arteries  in  general,  I  am  convinced 
that  it  is  a  frequent  development,  but  as  it  is  difficult  to  gauge  a 
normal  standard  of  thickness  for  each  coat  in  every  vessel,  the  esti- 
mation must  remain  a  relative  one,  influenced  by  the  personal  factor. 
Nor  is  it  possible  to  give  any  opinion  as  to  hypertrophy  by  counting 
the  number  of  muscle  layers  between  the  two  elastic  laminae.  With 
Aschoff  we  must  agree  that  there  is  a  progressive  increase  in  the  size 
and  quality  of  the  arterial  coats  with  advancing  years  up  to  the  age 
of  thirty-five.  This  has  recently  been  verified  in  our  laboratory  by 
Foster  working  under  me  at  the  Royal  Victoria  Hospital.  This 
physiological  development  in^'olves  all  the  tissues  in  the  coat, 
although  the  elastic  fibres  and  the  muscle  cells  form  the  important 
elements  in  the  media. 

Jores  in  his  studies  on  arteriosclerosis,  in  which  he  placed  so 
much  stress  upon  the  development  of  elastic  fibres  in  the  intima, 
also  made  some  observations  on  the  development  of  new  elastic 
tissue  in  the  media.  He  found  that  where  the  intima  showed  such 
a  development  of  elastic  fibres,  the  media  also  partook  of  this 
change.  On  the  other  hand,  he  did  not  observe  the  development 
of  elastic  fibres  in  the  media  where  the  intima  remained  unchanged, 
nor  were  these  fibres  to  be  observed  in  instances  of  progressive 
mesarteritis. 

Meigs  is  of  the  opinion  that  the  hypertrophied  condition  of  the 
media  is  a  diseased  and  degenerative  state.  He  has  noted  the  in- 
crease in  the  number  of  muscle  cells  of  the  media,  but  he  finds  that 
this  is  associated  with  a  breaking  down  of  the  muscle  fibres  and 
other  evidences  of  degeneration. 

Arteries  with  a  thickened  media  are  readily  subject  to  processes 
of  disease.  Whereas,  the  process  of  hypertrophy  was  stimulated 
by  an  increase  in  function,  at  a  time  when  the  necessary  extra  nutri- 


Diseases  Affecting  the  Media.  21 

tion  was  available,  the  body  sooner  or  later  meets  with  circum- 
stances in  which  either  the  nutrition  is  not  properly  maintained  or 
in  which  the  stimuli  acting  on  the  media  become  greater  than  can 
be  sustained,  with  a  resulting  ill-efifect  on  this  coat.  On  the  other 
hand  too,  if  this  increased  function  consist  of  excessive  pressure 
within  the  artery  hypertrophy  continues  for  some  time,  until  the 
media,  the  mainstay  of  the  artery,  becomes  exhausted  and  can  no 
longer  become  hypertrophied  nor  give  rise  to  new  tissue  cells.  Such 
exhausted  cells  allow  the  vessel  to  dilate,  and  themselves  undergo 
destruction.  This  process  of  early  hypertrophy  with  a  later  degen- 
eration can  be  readily  followed  in  the  femoral  arteries.  In  different 
subjects  all  stages  of  hypertrophy,  exhaustion,  dilatation  and  degen- 
eration are  to  be  found.  The  many  sacculations  found  in  the 
vessels  of  the  muscular  type,  in  Moenkeberg's  arteriosclerosis,  are 
aneurysmal  pouchings  which  have  passed  through  the  above  stages. 

Concerning  the  hyperplasia  in  the  renal  arterioles  there  is  still 
much  debate.  The  question  arises  whether  the  arterial  hypertrophy 
in  chronic  Bright's  disease,  arises  before  or  in  consequence  of  the 
interstitial  fibrosis  and  hyaline  changes  in  the  glomeruli.  This 
question  can  only  be  answered  by  considering  the  mechanics  of  the 
structures  under  discussion.  Moreover  under  different  circum- 
stances other  factors  have  a  decided  bearing  on  the  subject. 

Looking  at  the  glomerulus  from  a  mechanical  point  of  view  I 
should  think  that  it  is  of  enormous  importance  that  so  delicate  a 
mechanism  should  not  be  subjected  to  a  sudden  rise  of  blood  pres- 
sure, nor  to  a  continued  and  excessive  pressure.  In  themselves  the 
glomeruli  are  unable  to  exert  any  controlling  influence  on  the  blood 
pressure.  Hence  this  control  must  fall  on  the  smaller  branches  of 
the  renal  arteries  and  their  arterioles.  The  higher  the  mean  arterial 
pressure,  the  greater  is  the  nefed  for  contraction  of  these  arteries, 
and  the  greater  is  the  tendency  to  muscular  hypertrophy  to  reduce 
the  glomerular  blood  supply.  Whether  these  arteries  contract 
owing  to  reflex  nervous  stimuli  or  to  the  direct  action  of  substances 
of  the  adrenalin  type  must  at  present  be  left  an  open  question. 

In  this  we,  therefore,  agree  with  Johnson  that  a  true  medial 
hypertrophy  is  found  in  nephritis.  Johnson,  however,  assumes  a 
kidney  lesion  antecedent  to  the  arterial  changes.     His  own  summary 


22  Arteriosclerosis.    Diseases  of  the  Media. 

states  his  position  very  clearly.  "  In  consequence  of  the  degenera- 
tion of  the  kidney  the  blood  is  morbidly  changed.  It  contains 
urinary  excreta  and  is  deficient  of  some  of  its  own  normal  consti- 
tuents. It  is,  therefore,  more  or  less  unsuited  to  nourish  the  tissues, 
more  or  less  noxious  to  them.  The  minute  arteries  throughout  the 
body  resist  the  passage  of  this  abnormal  blood.  The  left  ventricle 
makes  therefore  an  abnormal  effort  to  drive  on  the  blood.  The 
result  of  this  antagonism  of  forces  is  that  the  muscular  walls  of 
the  arteries  and  of  the  left  ventricle  of  the  heart  become  simultan- 
eously and  in  an  equal  degree  hypertrophied.  The  persistent  over 
action  of  the  muscular  tissues,  both  cardiac  and  arterial,  is  registered 
after  death  in  a  conspicuous  and  unmistakable  hypertrophy." 

Gull  and  Sutton  do  not  agree  with  Johnson.  They  believe  that 
the  arterial  changes  in  the  kidney  are  conditions  common  to  all 
arteries  of  equal  size  which  are  or  may  be  independent  of  renal 
disease.  In  other  words  the  lesions  in  the  vessels  of  the  kidney  are 
only  a  part  of  a  generalized  condition. 

I  do  not  believe  that  in  all  cases  the  hypertrophy  of  the  media 
increases  the  resisting  and  contractile  powers  of  the  vessels.  Where 
the  process  is  a  physiological  one,  as  in  the  uterus,  the  hypertrophy 
becomes  essential  to  carry  on  the  increased  work  to  which  the 
vessels  are  subjected.  Pregnancy  demands  vastly  greater  blood 
supply  than  normally  passes  to  the  uterus,  and  to  this  increased 
supply  the  arteries  must  accommodate  themselves.  But  once  the 
physiological  increase  of  supply  is  at  an  end,  the  arteries  must  again 
accommodate  themselves  to  an  inferior  work.  The  vessel  walls 
then  contain  a  larger  quantity  of  tissue,  particularly  muscular  ele- 
ments in  the  media,  than  is  required  for  the  normal  functions,  and 
these  elements  which  are  thrown  into  disuse  are  those  which  become 
subject  to  atrophy  and  degeneration.  Hence  in  these  same  arteries 
where  we  not  infrequently  note  true  hypertrophies  and  hyperplasias 
we  also  observe  processes  of  degeneration  without  any  sign  of 
tissue  reaction. 

Acute  Mesarteritis. — Acute  mesarteritis  is  rather  an  unusual  type 
of  arterial  disease  unless  especially  looked  for  with  the  aid  of  the 
microscope.  It  is  but  the  rare  case  which  is  detected  by  the  naked 
eye,  unless  the  condition  has  advanced  to  such  a  degree  as  to  produce 


Diseases  Affecting  the  Media.  23 

pus  foci  in  the  walls  of  the  arteries.  On  the  other  hand  acute 
inflammatory  conditions  are  present  in  the  media,  in  cases  of  my- 
cotic aneurysms,  such  as  have  been  described  by  McCrae.  These 
cases  show  microscopic  evidence  of  severe  disorganization  of  the 
entire  vessel  wall,  without  the  evidence,  which  one  looks  for  in  cases 
of  aneurysm,  of  chronic  changes  accompanied  by  an  endarteritis. 

Not  uncommonly  too,  the  acute  progressive  stage  of  mesarteritis 
is  seen  to  accompany  lesions  more  advanced  in  repair.  Syphilitic 
aortitis  shows  very  often  the  progressive  inflammation  of  the  media 
and  adventitia  about  the  vasa  vasorum,  while  irregularly  scattered 
through  the  vessel  are  plaques  of  fibrosis  denoting  a  previously 
acute  process.  I  have  only  once  obtained  a  specimen  of  acute 
syphilitic  mesaortitis  which  did  not  show  any  evidence  of  chronicity 
(fibrosis).  The  specimen  was  obtained  from  a  luetic  who  died  in 
the  late  secondaries  from  an  accident.  Macroscopically  in  this  case 
no  evidence  was  present  indicating  disease  of  the  aorta — and  only 
in  section  were  the  lymphocytic  collections  about  the  vasa,  and  the 
new  formation  of  capillaries  in  the  outer  part  of  the  media,  indi- 
cated. It  is  to  be  considered  that  in  every  case  of  syphilitic  arteritis 
there  is  an  acute  or  subacute  stage  in  which  the  media  forms  one  of 
the  principal  foci.  I  have  twice  been  successful  in  demonstrating 
the  SpirochcBta  pallida  in  these  specimens  and  others  have  also 
reported  this  finding. 

Not  infrequently  a  slight  and  transient  acute  mesarteritis  is 
present  in  typhoid  (Landouzy  and  Siredey)  and  streptococcus  septi- 
caemias. The  conditions  in  the  media  in  these  diseases  is  quite  inde- 
pendent of  any  changes  which  may  be  present  in  the  intima. 
Accompanying  a  streptococcus  septicaemia  an  inflammatory  condi- 
tion of  greater  or  lesser  degree  is  formed  in  association  with  the 
small  nutrient  vessels  of  the  adventitia  and  the  media,  while  quite 
apart  from  these  changes  and  isolated  in  areas  of  the  intima  away 
from  the  infiltrated  tissue  of  the  media,  are  commonly  seen  super- 
ficial fatty  streaks.  These  superficial  fatty  degenerations  of  the 
intima  are  found  in  the  aorta  between  the  pairs  of  mouths  of  the 
intercostal  branches.  The  significance  of  these  fatty  streaks  is  still 
under  debate  although  Aschoff  favors  the  view  that  these  are  the 
early  stages  of  arteriosclerosis.     This  much,  however,  we  can  say. 


24  Arteriosclerosis.    Diseases  of  the  Media. 

that  the  intimal  fatty  streaks  are  not  dependent  on  the  inflammatory 
lesions  about  the  vasa  of  the  media. 

Thorel  has  found  that  in  acute  infectious  diseases  the  larger 
arteries  show  a  small-celled  infiltration  of  the  adventitia.  Of  these 
diseases  typhoid,  scarlet  fever  and  diphtheria  are  most  frequently 
associated  with  this  form  of  arteritis. 

It  has  been  a  fairly  common  observation  among  clinicians  to  find 
thromboses,  particularly  in  the  arteries  of  the  lower  extremities 
in  cases  of  typhoid  fever.  These  lesions  have  been  particularly 
commented  upon  by  the  French  observers.  More  recently,  however, 
Thayer  has  made  a  thorough  study  of  thromboses  in  typhoid  fever, 
and  has  laid  particular  stress  upon  its  association  with  acute  mesar- 
teritis.  He  was  able  to  demonstrate  an  acute  arteritis  preceding  the 
thrombosis. 

Moreover,  this  author  observed  that  the  "  radial  arteries  in  old 
typhoids  were  palpable  in  a  proportion  nearly  three  times  as  great  as 
that  found  in  control  observations." 

McCrae  has  recently  demonstrated  acute  lesions  in  the  media  due 
to  the  streptococcus  in  the  course  of  a  puerperal  infection.  In  his 
case,  however,  there  was  present  a  progressive  syphilitic  aortitis, 
and  it  was  found  that  in  the  areas  of  syphilitic  arterial  change  the 
secondary  streptococcal  invasion  was  the  most  recent  and  produced 
further  medial  degenerations,  thereby  hastening  the  development  of 
aneurysm  at  these  sites. 

A  mesarteritis  is  commonly  present  in  vessels  passing  to  or  in  the 
neighborhood  of  infected  and  purulent  foci.  Larger  arteries  lying 
near  a  small  abscess  may  have  only  half  of  their  circumference  or  less 
showing  acute  inflammatory  infiltration.  The  process  of  inflamma- 
tion may  be  localized  along  the  vessels  of  the  media  or  the  condi- 
tion may  be  diffuse  and  without  regard  to  the  blood  supply  of  the 
vessel  coats.  Such  vessels  are  most  commonly  seen  in  the  lungs  in 
association  with  infected  tuberculous  cavities  (Pauli).  Of  neces- 
sity these  conditions  will  also  lead  to  inflammatory  processes  in  the 
adventitia.  The  importance  of  an  acute  mesarteritis  associated 
with  abscess  formation  is  that  the  vessel  wall  lying  contiguous  to  the 
abscess  cavity  undergoes  necrosis,  with  possible  aneurysm  forma- 
tion, and  at  times  there  is  rupture  of  the  artery.     Such  a  degenera- 


Diseases  Affecting  the  Media.  25 

tion  of  the  vessel  wall  may  result  as  a  direct  advance  of  the  necrotic 
process  into  the  arterial  tissues,  or  from  a  septic  thrombus  of  the 
vasa  vasorum. 

It  may  be  well  to  note  here,  that  this  process  explains  the  pres- 
ence of  aneurysms  in  and  about  tuberculous  cavities  in  the  lung. 

Less  frequently  one  meets  with  an  acute  inflammatory  process 
advancing  from  the  intima  into  the  media.  Such  cases  are  asso- 
ciated with  the  deposition  of  a  septic  thrombus  on  the  surface  of  the 
intima  and  are  usually  located  at  the  site  of  atheroma  or  athero- 
matous ulceration  (thromboarteritis).  In  the  aorta,  mural  thrombi 
are  not  so  rare;  in  the  peripheral  arteries,  however,  the  thrombi 
more  frequently  encircle  the  entire  vessel  and  occlude  it.  In  each 
of  these  types  the  septic  agents  may  advance  through  the  intima  into 
the  media  and  there  set  up  an  acute  inflammation  with  a  diffuse  poly-, 
nuclear  infiltration.  It  is  obvious  that  the  presence  of  a  septic  em- 
bolus may  lead  to  results  in  the  vessel  coats,  similar  to  thrombosis. 

Mechanical  injury  without  the  presence  of  sepsis  is  also  an  occa- 
sional factor.  Not  a  few  cases  are  on  record  of  traumatic  injury, 
by  bullets,  of  one  or  other  of  the  arterial  coats,  and  in  all  of  these 
cases  presenting  a  secondary  aneurysm  from  such  an  injury,  the 
media  has  been  severely  damaged. 

The  histological  appearance  of  these  vessels  differs  but  slightly. 
There  are,  however,  the  cases  in  which  the  acute  inflammatory  infil- 
tration of  the  media  is  diffuse  while  in  others  it  is  localized  to  the 
small  nutrient  vessels  passing  from  the  adventitia  into  the  outer 
third  of  the  middle  coat.  Again  of  the  latter  group  there  are  those 
in  which  the  inflammatory  infiltration  is  for  the  most  part  made  up 
of  lymphocytes,  as  in  syphilis  and  the  chronic  granulomata,  while 
others  are  almost  entirely  polymorphonuclear  leucocytes.  Save  for 
the  granulomatous  lymphocytic  infiltrations,  the  character  of  the  in- 
flammatory process  gives  us  but  little  information  as  to  the  nature 
of  the  infecting  agent.  To  this  I  m.ust  add,  however,  that  in  acute 
mesarteritis  of  the  vessels  at  the  base  of  the  brain,  and  particularly 
in  meningococcus  infections  the  leucocytic  infiltration  is  most  in- 
tense and  diffuse — at  times  so  extensive  as  to  overshadow  the  tissue 
of  the  individual  layers  of  the  wall.  The  picture  is  a  very  striking 
one,  showing  the  invasion  of  the  leucocytes,  not  by  way  of  the  blood 


26  Arteriosclerosis.    Diseases  of  the  Media. 

stream,  but  by  the  lymphatic  spaces.  The  question  of  meningo- 
coccus arteritis  is  well  discussed  by  Loewenstein. 

In  the  lesions  produced  by  severe  typhoid  fever,  the  areas  of 
leucocytic  infiltration  in  the  media  may  show  evidence  of  connective 
tissue  proliferation.  In  these  it  is  seen  that  the  cells,  immediately 
surrounding  the  vasa  vasorum,  become  large  and  oval  shaped,  and 
between  these,  cells  of  fibroblast  types  are  seen.  At  times  too  these 
areas  of  proliferation  are  seen  to  extend  closer  to  the  intima  than 
the  normal  position  of  the  vasa  would  take  them.  The  intima 
commonly  shows  only  a  slight  proliferation  of  the  endothelial  cells, 
with,  however,  quite  a  marked  fatty  degeneration  of  the  musculo- 
elastic  layer.  In  the  more  severe  typhoid  infections  the  muscle  cells 
of  the  media  show  signs  of  extensive  degeneration  with  a  fine  fatty 
deposit  in  them.  These  changes  accompanied  by  a  productive 
process  are  most  often  seen  in  the  vessels  of  the  elastic  type.  In  a 
number  of  cases  the  bacteria  present  in  the  arterial  walls  have  been 
demonstrated  by  appropriate  methods  (Warthin  and  McCrea). 

In  none  of  the  lesions  of  the  acute  inflammatory  type  have  I  ever 
noted  evidence  of  new  elastic  tissue  formation. 

Experimentally  various  inflammatory  lesions  have  been  produced 
in -the  media  by  infective  agents  (Klotz  and  Saltykow),  trauma, 
(Malkoff)  and  thrombi.  In  introducing  living  bacteria  into  the 
circulation,  these  organisms  find  their  way  into  the  vasa  vasorum 
and  set  up  inflammatory  conditions  about  them.  The  histological 
picture  is  identical  with  that  found  in  human  arteries  in  which 
infection  has  gained  entrance  into  the  medial  tissues.  Syphilitic 
mesarteritis  has  not  been  reproduced  in  animals. 

The  so-called  neurotic  angioscleroses  (Lewaschew)  produced  in 
dogs  by  injury  and  division  of  the  sciatic  nerve  must  be  regarded 
as  an  infective  lesion  following  trophic  ulcers  of  the  leg.  Lewa- 
schew found  inflammatory  lesions  in  the  media  and  adventitia  of  the 
smaller  arteries,  but  no  changes  in  the  larger  vessels.  In  some  of 
the  animals  experimented  upon  gangrene  of  the  leg  or  extensive 
ulcers  developed,  which  were  no  doubt  associated  with  the  general 
cellulitis  and  arteritis  present  (Czyhlarz  and  Helbring). 

An  acute  mesarteritis  is  a  serious  lesion  in  the  vessel  wall,  and 
particularly  that  type  which  is  persistent  and  in  which  considerable 


Diseases  Affectmg  the  Media.  27 

destruction  (as  in  syphilis),  accompanies  the  inflammation. 
Aneurysms  both  of  rapid  or  slow  development  are  serious  possi- 
bilities. The  milder  grades  of  mesarteritis  usually  mend  readily, 
leaving  more  or  less  connective  tissue  at  the  points  of  repair. 

The  final  stages  of  acute  mesarteritis  will  be  considered  under 
Chronic  Mesarteritis. 

Chronic  or  Productive  Mesarteritis. — Most  of  the  cases  of 
chronic  productive  mesarteritis  have  had  a  preceding  acute  stage, 
and  the  majority  owe  their  being  to  infection.  Odd  cases,  no 
doubt,  are  met  with  in  which  a  true  acute  stage  was  lacking,  and 
which  from  the  very  first  were  slowly  progressive — of  the  nature  of 
chronic  granulomata  or  in  which  a  replacement  fibrosis  followed 
non-inflammatory  degenerations.  However,  it  may  be  said  in 
general,  that  those  factors  which  produce  an  acute  mesarteritis,  as 
was  noted  above,  are  also  able  to  produce  chronic  fibrosis  of  the 
media. 

The  chronic  inflammatory  conditions  of  the  media,  and  it  is  true 
also  of  the  acute  inflammations,  are  more  commonly  found  in  the 
aorta  and  its  large  branches  than  in  any  other  vessels  in  the  body. 
The  reason  for  this  lies  in  the  abundant  capillary  supply  to  the  outer 
portion  of  the  media  of  the  aorta  and  the  large  arteries,  while  in 
the  smaller  vessels  these  nutrient  vessels  are  few  or  entirely  want- 
ing. In  1844  Rokitansky  stated  that_the  intima  of  blood  vessels 
could  not  become  inflamed,  because  of  the  lack  of  blood  capillaries. 
To-day  we  recognize  an  inflammatory  condition  of  non-vascular 
tissues,  and  we  may  modify  Rokitansky's  maxim,  and  say  that  the 
frequency  of  inflammatory  states  of  the  arterial  coats  is  directly 
dependent  upon  the  vascularity  of  the  vessel  walls. 

All  are  fully  agreed,  I  believe,  that  we  must  distinguish  between 
the  primary  and  secondary  mesaortitis  (and  also  mesarteritis),  as 
has  been  fully  set  forth  by  Chiari.  We  would  suggest,  however, 
that  whereas  Chiari  has  distmguished  between  two  types  of  medial 
disease  occurring  in  the  aorta,  his  Type  A  and  Type  B  can  and 
should  be  applied  to  the  productive  mesarteritis  whenever  it  is 
found.  The  features,  which  distinguish  the  primary  from  the 
secondary  production  of  the  scar  tissue  in  the  aorta,  are  applicable 
to  all  the  arteries. 


28  Arteriosclerosis.    Diseases  of  the  Media. 

The  secondary  mesarteritis  or  Chiari's  type  A  is  the  result  of, 
and  follows  a  diseased  condition  of  the  intima,  an  endarteritis 
chronica  deformans.  In  this  instance  the  mesarteritis  is  limited 
to  the  area  underlying  a  hyperplastic  intimal  plaque  or  an  athero- 
matous softening.  In  this  isolated  area  of  the  media  the  vasa 
vasorum  advance  from  the  outer  third  of  the  media  towards  the 
intima.  Evidently  the  cutting  off  of  the  nourishment  from  the 
intima  by  the  endarteritis  has  been  a  sufficient  stimulus  to  lead  to 
new  capillar}^  formation.  These  A'essels  are  surrounded  by  a  leu- 
cocytic  infiltration  and  later  heavy  strands  of  connective  tissue 
occupy  their  environment.  With  the  advance  of  the  vasa  vasorum 
and  the  accompanying  fibrosis,  the  tissue  elements  of  the  media 
are  pushed  aside  and  distorted.  The  concentric  elastic  bands  are 
interrupted  in  their  course  and  the  muscle  fibres  are  replaced  by  con- 
nective tissue.  Similar  changes  are  also  to  be  found  in  the  adven- 
titia,  where  it  is  well  seen  how  the  chronic  inflammatory  or  pro- 
ductive tissue  follows  the  course  of  the  blood  vessels. 

It  is,  however,  less  frequent  to  find  a  productive  mesarteritis 
following  intimal  sclerosis,  than  to  observe  degenerative  changes 
occurring  in  the  media  underneath  endarteritic  plaques  or  atherom- 
atous ulcerations.  However,  in  the  event  of  an  adherent  throm- 
bus in  an  artery  becoming  organized,  the  fibrous  tissue  elements 
which  invade  the  thrombus  from  the  intima,  also  extend  down- 
wards into  the  media.  Moreover  the  nutrient  supply  for  the  or- 
ganizing mass  is  obtained  to  a  great  extent  from  the  vasa  vasorum 
of  the  media.  These  vessels  send  capillaries  to  the  organizing  clot, 
and  along  with  them  there  is  a  considerable  development  of  fibrous 
tissue.  In  the  event  of  a  later  canalization  of  the  thrombus,  the 
walls  of  the  artery  remain  permanently  sclerosed  at  this  point. 

In  Chiari's  productive  mesarteritis.  Type  B,  which  term  he  re- 
serves particularly  for  syphilitic  mesaoritis,  the  chronic  inflamma- 
tion and  connective  tissue  proliferation  in  the  media  are  primary 
to  any  changes  occurring  in  the  intima.  The  changes  which  occur 
in  the  media  and  adventitia  constitute  the  important  characteristics 
of  the  disease,  while  the  intimal  thickening  is  only  developed  sec- 
ondarily. Type  B  is  particularly  characterized  by  the  infrequency 
of  degenerative  changes  (calcification)  arising  in  the  intima,  while 


Diseases  Affecting  the  Media.  29 

however,  this  thickened  layer  is  furrowed  and  "  knotty,"  and  is 
localized  mainly  in  the  ascending  aorta.  Microscopically,  the  im- 
portant changes  are  found  in  the  media,  where  granulation  tissue 
and  connective  tissue  form  firm  masses  about  the  vasa  vasorum 
such  as  are  not  present  in  endarteritis  chronica  deformans.  The 
adventitia  always  shows  more  or  less  inflammatory  reaction  about 
the  vasa,  while  the  intima  after  a  time  proliferates,  after  the  nature 
of  a  chronic  inflammation.  It  is  seldom  that,  early  in  the  disease, 
macroscopic  degenerative  processes  appear  in  the  media,  or  if  they 
do,  they  are  very  slight  in  extent.  The  lesions  appear  in  their 
whole  nature  to  be  the  result  of  a  chronic  irritation,  which  is  only 
sufficiently  severe  to  stimulate  growth.  That  a  certain  quantity  of 
muscle  and  elastic  tissue  is  destroyed  in  the  media  during  the  prog- 
ress of  the  inflammation  is  not  to  be  denied,  but  the  loss  of  this 
tissue  is  sufficiently  slow  to  allow  the  growth  of  the  connecti^^e 
tissue  to  fill  in  many  of  the  gaps. 

In  the  more  advanced  conditions  where  the  inflammatory  process 
has  spread,  the  old  sites  of  invasion  give  place  to  "  gummy  "  de- 
generation in  which  the  muscle  and  elastic  tissue  appear  to  melt 
away.  The  involved  vessel  wall  is  much  distorted,  and  its  place 
taken  by  granulation  tissue,  fibrosis  and  necrosis. 

I  shall  discuss  later  the  point  about  which  there  has  been  some 
debate,  namely,  whether  the  intimal  change  here  is  to  be  regarded 
as  the  outcome  of  the  chronic  inflammation  or  as  of  the  nature  of 
a  strain  hypertrophy. 

We  have  now,  thanks  to  Francis  Welch  and  Heller,  become 
familiar  with  the  macroscopic  picture  of  syphilitic  aortitis,  so  that 
it  seldom  escapes  recognition.  The  localization  in  the  ascending 
aorta,  the  lack  of  certain  degenerative  changes  on  the  surface,  the 
furrowed,  thickened  and  scarred  intima  combine  to  form  an  un- 
mistakable picture.  With  the  microscopic  picture  of  the  intima  I 
do  not  believe  we  can  be  so  certain.  There  are  other  infectious 
diseases  which  lead  to  a  small  celled  infiltration  of  the  vasa  vas- 
orum in  the  adventitia  and  media,  and  which  on  healing  leave 
bands  of  scar  tissue  coursing  through  the  tissues  of  the  vessel  wall. 
However,  the  characteristics  of  syphilitic  mesarteritis  bear  the 
same  relationship  to  those  of  other  infectious  mesarteritides  as  the 


30  Arteriosclerosis.    Diseases  of  the  Media. 

syphilitic  cirr hoses  of  the  liver  do  to  other  liver  cirrhoses.  That  is 
in  syphilitic  mesarteritis  the  connective  tissue  bands  are  much 
heavier,  and  more  stellate  than  are  seen  in  other  cases. 

The  macroscopic  appearance  of  the  syphilitic  aorta  in  the  ad- 
vanced stage  is  well  described  by  Malmsten.  "The  v^all  of  the 
aorta  is  thickened.  The  inner  surface  is  uneven  and  has  diffuse 
or  closely  aggregated,  round  or  irregular,  more  or  less  circum- 
scribed convex  plaques,  which  on  cutting  through  are  seen  to  consist 
of  yellowish  white  firm  masses,  presenting  here  and  there  stellate 
scar-like  contractions.  This  puckering  leads  to  the  irregular  groov- 
ings  and  warty  character  of  the  surface.  Besides  this  sclero- 
gummy  process,  the  aorta  shows  changes  simulating  advanced  and 
degenerated  syphilitic  lesions  elsewhere.  As  regards  the  localiza- 
tion, the  aorta  may  be  attached  throughout  its  entire  length  or  more 
frequently  in  the  ascending  arch  alone,  or  again  various  areas  in  the 
vessel  may  be  attacked  leaving  clear  parts  between  the  lesions. 
Large  calcareous  masses  or  plaques  are  entirely  wanting." 

In  short,  in  this  stage  of  syphilitic  aortitis  all  three  coats  of  the 
artery  are  affected,  the  intimal  lesions  having  followed  the  changes 
in  the  adventitia  and  media.  Microscopically  we  find  that  the 
thickened  artery  owes  its  bulk  to  the  immense  increase  in  the  ad- 
ventitia along  with  the  thickening  of  the  intima.  The  media  suffers 
an  actual  loss  and  narrowing  due  to  destruction  of  the  fibres  of  its 
essential  tissues,  and  is  frequently  reduced  to  less  than  one  third 
its  original  width. 

As  we  have  stated  above,  the  early  changes  in  syphilitic  arteritis 
takes  place  about  the  vasa  vasorum  of  the  adventitia,  of  the  nature 
of  lymphocytic  infiltration  about  the  arterioles  and  capillaries.  Tis- 
sue destruction  is  not  evident  at  the  beginning.  Lymphocytic  infil- 
trations about  the  vasa  vasorum  are  also  seen  very  early,  and  with 
this  there  appears  a  new  development  of  capillaries  which  course 
the  media  beyond  the  limits  of  the  outer  third.  As  these  vessels 
stretch  through  the  medial  tissues  there  is  a  concurrent  loss  of 
muscle  and  elastic  tissue,  while  young  fibrous  tissue  accompanies 
the  advance  of  the  vasa.  The  remarkable  feature  in  the  process 
of  the  lesion  is  the  rapid  disappearance  of  the  fixed  tissues  (muscle 
and  elastic  fibres).     These  tissues  appear  to  melt  away  in  the  en- 


Diseases  Affecting  the  Media.  31 

vironment.  of  the  syphilitic  virus,  but  tlie  process  of  tissue-loss  is 
not  so  rapid  as  to  leave  areas  of  necrosis  patent,  but  new  fibrous  tis- 
sue is  found  to  keep  almost  equal  pace  with  the  tissue  destruction. 
The  areas  in  which  the  tissue  cells  are  "  melting  dow^n,"  are  always 
densely  infiltrated  with  lymphocytes,  plasma  cells  and  fibroblasts. 
A  careful  examination  of  active  syphilitic  lesions  in  the  arterial 
wall  demonstrates  that  the  muscle  fibres  commonly  undergo  fatty 
degeneration  before  disintegrating,  and  that  similar  changes  take 
place  in  the  elastic  tissue.  Before  final  dissolution  the  elastic 
strands  no  longer  react  to  elastin  stains. 

The  vasa  vasorum  of  the  adventitia  and  media  frequently  show 
changes  quite  similar  to  those  in  the  main  artery  (Molinari).  The 
intimal  proliferation  in  these  small  vessels  becomes  so  great  as  to 
lead  to  occlusion  of  the  lumen,  and  ]\Iolinari  believes  that  this  pro- 
duces nutritional  disturbances  sufficient  to  cause  necrosis  of  the 
muscular  and  elastic  elements  of  the  media.  The  development  of 
granulation  tissue  and  miliary  nodules  about  the  vasa  vasorum  is 
considered  by  Doehle,  Beck  and  Backhaus  to  be  miliary  gummata. 
It  is  but  seldom  that  giant  cells  are  encountered  in  these  cellular 
aggregations. 

This  microscopic  picture  of  productive  mesarteritis  differs 
widely  from  the  ordinary  one  of  arteriosclerosis,  while  at  the  same 
time  it  is  quite  distinctive  for  syphilis  as  seen  in  the  aorta.  Nev- 
ertheless, it  must  be  remembered  that  other  agents  (infections) 
than  syphilis  can  bring  about  similar  changes  in  the  arteries.  Thus 
in  several  instances  Chiari  and  also  Beck  encountered  lesions  of  a 
like  nature  in  individuals  in  whom  both  the  history  and  the  anatom- 
ical findings  elsewhere  in  the  body  proved  negative  for  syphilis. 
Chiari  states  that  although  a  mesaortitis  productiva  of  the  Type  B 
may  be  caused  by  other  agents,  syphilis  as  a  factor  must  not  be 
lost  sight  of  in  any  case. 

Besides  producing  scar  tissue  in  the  media  with  a  secondary  pro- 
liferation in  the  intima,  syphilis  may  lead  to  true  gummatous  for- 
mation in  the  arteries.  Benda  and  others  have  observed  that  the 
small  and  medium  sized  arteries  as  well  as  the  thoracic  aorta  are 
the  places  most  often  attacked.  The  gummata  localize  in  the  media 
or  adventitia,  where  giant  cells  and  lymphocytic  infiltrations  are 


32  Arteriosclerosis.    Diseases  of  the  Media. 

found.  In  the  intima  the  endothehal  and  subendotheHal  tissues 
proliferate,  leading  to  endarteritis,  deformans  or  obliterans.  This 
tertiary  lesion  of  syphilis  in  the  aorta  has  also  received  attention 
from  Doehle  and  Malmsten,  the  latter  of  whom  referred  to  it  as  a 
"  sclerogummyaortitis."  The  gummy  type  of  lesion  carries  with  it 
the  characteristics  of  granulation  tissue  in  the  centre  of  which  the 
gummy  degeneration  is  found.  Hence  we  have  the  combined  pro- 
ductive and  degenerative  processes  going  on  side  by  side. 

The  more  direct  proof  of  the  nature  of  the  productive  mesarteri- 
tis  Type  B  being  syphilitic  has  been  brought  forward  by  Schmorl, 
Benda  Wright  and  me  in  the  demonstration  of  the  Spirochceta 
pallida  in  the  medial  lesions  of  the  arteries.  The  same  difficulty 
is  experienced  in  demonstrating  the  spirochsetes  in  the  syphilitic 
mesarteritis  as  is  found  with  the  tertiary  lesions  of  the  disease.  In 
favorable  instances  and  earlier  lesions  the  spirochsetes  are  present 
in  large  numbers  about  the  lymphocytic  collections  of  the  vasa. 
When  older  and  more  advanced  changes  are  present  the  organisms 
are  found  only  rarely  in  the  peripheral  zone. 

It  is  unquestionable  that  the  organism  (Spirochceta  pallida)  and 
its  toxins  are  directly  responsible  for  the  invasive  inflammatory 
tissue  of  the  adventitia  and  media. 

Up  to  the  present,  adequate  explanations  have  not  been  given  for 
the  localization  of  the  syphilitic  aortic  lesions  in  the  ascending  limb. 
The  frequency  of  this  site  suggests  an  anatomical  reason,  possibly 
depending  upon  the  nature  of  the  blood  supply,  and  the  origin  of 
the  vasa  vasorum  of  this  portion  of  the  aorta. 

While  so  many  observations  have  been  made  upon  the  histology 
of  acquired  syphilitic  aortitis,  there  had  been  relatively  little  work 
done  on  changes  in  the  arteries  in  the  congenital  form  of  the 
disease. 

Mracek  has  noted  in  congenital  syphilis  that  there  are  numerous 
ecchymoses  in  the  adventitia  of  the  larger  vessels,  while  the  vasa 
vasorum  exhibit  a  small-celled  infiltration  about  them.  Occasion- 
ally too,  he  noted  a  slight  endarteritis  in  the  carotid,  crural  and  iliac 
arteries.  Buchta  has  reported  a  case  of  congenital  syphilis  in  a 
young  adult  of  seventeen,  in  whom  the  vessels  of  the  arms  and 


Diseases  Affecting  the  Media.  33 

legs  became  cord-like,  and  greatly  impeded  the  circulation,  so  that 
partial  gangrene  of  the  foot  set  in. 

Bruhns  has  recently  examined  nine  cases  of  congenital  syphilis, 
and  has  been  able  to  demonstrate  lesions  in  the  aorta  which  are  very 
like  the  lesions  met  with  in  mesaortitis  productiva,  as  described  by 
Chiari  in  adults.  The  dilated  vasa  vasorum  in  the  adventitia 
showed  a  constant  small-celled  infiltration  about  them,  while  the 
condition  was  also  to  be  traced  in  the  outer  zone  of  the  media.  The 
dense  inflammatory  infiltration  of  the  media  leads  to  a  pushing 
apart  of  the  elastic  fibres,  so  that  the  structure  of  the  vessel  be- 
comes looser  in  this  region.  The  leucocytic  collections  in  his  spe- 
cimens consisted  both  of  mononuclear  and  poly  nuclear  cells,  while 
epithelioid  cells  were  also  present. 

Bruhns  concludes  that,  in  congenital  syphilis  of  the  aorta,  acute 
inflammatory  infiltrations  are  present  in  the  outer  layer  of  the  media 
and  in  the  adventitia,  particularly  about  the  vasa  vasorum.  He 
holds  that  the  lesions  of  congenital  syphilis  in  the  aorta  are  identical 
with  those  of  the  acquired  type  as  described  by  Chiari. 

Wiesner  has  studied  the  arterial  changes  in  ten  undoubted  cases 
of  congenital  syphilis  in  children,  and  has  found  constant  charac- 
teristic lesions  in  the  arteries.  According  to  his  findings  the  aorta 
with  its  larger  branches,  and  the  pulmonary  artery,  are  the  most 
frequent  sites  of  the  pathological  conditions.  In  these  vessels  he 
distinguished  a  boundary  zone  between  the  media  and  adventitia, 
in  which,  as  is  also  the  case  in  the  arterial  lesions  of  acquired 
syphilis,  the  primary  alterations  in  the  tissue  are  to  be  looked  for. 
He  found  a  constant  hypersemia  of  the  vasa  vasorum  both  in  the 
adventitia  and  in  the  boundary  zone,  while  in  some  cases  a  throm- 
bosis, and  even  a  hemorrhage,  occurred  in  these  regions.  The 
hemorrhages  in  his  cases  occurred  most  frequently  in  the  adventitia. 
Another  constant  feature  found  in  the  arteries  in  congenital  syphilis 
is  the  presence  of  a  round-cell  infiltration  following  the  vasa  vas- 
orum from  the  adventitia  into  the  media.  In  congenital  syphilitic 
children  several  wrecks  old,  Wiesner  found  a  peri-vascular  fibrosis 
replacing  the  cellular  infiltration,  and  in  some  cases  an  obliteration 
of  the  nutrient  vessels. 

In  one  instance  of  a  child  three  months  old  he  noted  the  occur- 


34  Arteriosclerosis.    Diseases  of  the  Media. 

rence  of  a  connective-tissue  production  in  the  media,  so  that  the 
elastic  fibres  had  almost  entirely  disappeared  in  this  region.  Wies- 
ner  considered  _that  this  was  a  later  stage  of  the  inflammatory  in- 
filtration seen  about  the  vasa  of  the  aorta  in  new  born  children. 

Recently  we  have  reported  a  case  of  congenital  syphilitic  aortitis 
in  a  still-born  full-term  child.  The  lesions  in  this  case  presented 
characters  similar  to  those  seen  in  the  acquired  disease.  The 
ascending  aorta  and  the  arch  were  the  site  of  irregular  radiating 
grooves  about  which  the  intima  was  thickened.  Petechial  hemor- 
rhages of  the  media  could  be  seen  through  the  intima. 

In  the  microscopic  sections,  it  was  found  that  the  media  showed 
an  intense  small  celled  infiltration,  localized  about  the  vasa  vaso- 
rum.  This  infiltration  was  also  present  in  the  adventitia.  Not 
alone  were  lymphocytes  present  about  the  vasa,  but  there  were 
polynuclear  and  epithelioid  cells,  besides  a  general  diffuse  fibrosis, 
pushing  aside  the  normal  tissues  of  the  wall.  A  necrosis  involving 
the  elastic  tissue  and  muscle  fibres  of  the  media  was  present.  The 
intima  was  much  thickened  over  the  altered  media. 

It  was  suggested  that  since  the  congenital  syphilitic  lesions  of  the 
aorta  resembled  so  closely  those  of  the  acquired  type  in  adults,  that 
more  than  probable,  some  of  the  so-called  acquired  lesions  in  the 
arteries  which  are  met  with  in  later  life,  are  of  congenital  origin, 

Recently  Scharpff  has  examined  the  aortas  from  a  number  of 
syphilitic  infants.  The  specimens  which  he  examined  showed  no 
macroscopic  lesions,  and  he  was  unable  to  determine  any  definite 
mesarteritis  in  the  histological  preparations.  From  his  observa- 
tions Scharpff  rather  doubts  the  findings  and  conclusions  of 
Wiesner. 

On  the  other  hand  Scharpff's  findings  only  illustrate  that  in 
cases  of  congenital  syphilis,  aortic  lesions  are  not  necessarily 
present.     The  same  is  also  true  for  acquired  syphilis. 

As  has  been  repeatedly  stated  above,  although  syphilis  is  the 
more  frequent  causative  factor  in  the  production  of  a  primary 
chronic  mesarteritis,  due  credit  must  be  given  to  other  infections. 
I  have  convinced  myself  that  rheumatism  does  lead  to  small  areas 
of  medial  fibrosis  which  in  many  respects  simulate  the  sclerotic 
patches  in  the  heart  described  by  Aschoft*.     During  the  progressive 


Diseases  Affecting  the  Media.  35 

stage  of  these  lesions  narrow  lines  of  cellular  infiltration  are  seen 
along  the  small  capillaries  in  the  adventitia  and  also  in  the  media. 
The  larger  arteries  and  arterioles  of  the  media  do  not  share  this 
infiltration.  Moreover  the  inflammatory  process  is  limited  to  a 
very  narrow  zone  just  along  the  vasa  vasorum.  Frequently  this 
infiltration  is  only  a  few  cells  deep.  As  the  process  of  repair 
advances  this  area  becomes  occupied  by  a  zone  of  fibrosis,  which  as 
in  rheumatic  myocarditis,  is  very  patchy  in  character.  Recently 
I  have  been  able  to  reproduce  these  lesions  in  rabbits  by  repeated 
inoculations  at  varying  intervals  of  the  so-called  Micrococcus 
rheumaticus.  These  experimental  lesions  I  found  only  in  the 
aorta,  and  in  some  instances  they  were  associated  with  intimal 
thickenings  in  the  aortic  arch. 

In  typhoid  infections  although  an  acute  stage,  as  we  have  de- 
scribed under  acute  mesarteritis,  is  not  infrequently  found,  the 
process  of  fibrosis  does  not  so  commonly  occur.  It  would  seem 
that  although  there  is  an  acute  reaction  about  the  vasa  vasorum  in 
typhoid,  the  reaction  is  too  slight,  and  the  fixed  tissues  about  the 
vasa  are  too  little  altered  to  demand  the  development  of  new  fibrous 
tissue.  It  was  only  rarely  that  there  was  any  evidence  of  destruc- 
tion or  of  fibrous  tissue  proliferation  about  the  vasa  vasorum. 

More. rarely  do  we  find  a  tuberculous  infection  of  the  media. 
Occasional  cases  of  tuberculosis  involving  the  intima  have  been 
'reported.  These  latter  conditions  are  most  frequently  found  asso- 
ciated with  a  previous  intimal  lesion  into  which  the  tubercle  bacilli 
have  found  their  way,  setting  up  a  caseating  focus  (Aschoff). 
Here  and  there  the  aortic  wall  is  involved  along  with  other  organs 
in  a  miliary  tuberculosis  which  can  be  recognized  by  the  naked  eye, 
and  the  infection  is  found  to  localize  in  the  intima  (Thorel). 
Blume  found  such  a  condition  in  the  pulmonary  veins  of  a  child  one 
and  three-quarters  years  old.  In  all  of  the  reported  cases  an  active 
or  caseating  focus  has  been  described  which  was  in  close  association 
with  or  had  broken  into  a  blood  vessel,  leading  to  a  severe  tubercu- 
lous septicaemia.  It  is  indeed  remarkable  that  in  the  event  of  a 
tuberculous  focus  existing  in  the  intima  of  an  artery,  it  is  seldom 
that  this  focus  extends  into  the  media.  Indeed  it  is  imusual  too 
that  an  isolated  tuberculous  focus  develops  about  the  vasa  vasorum 


36  Arteriosclerosis.    Diseases  of  the  Media. 

at  a  distance  from  the  primary  site.  Tubercles  may  and  do  form 
commonly  in  the  adventitia  of  the  arteries  lying  in  tuberculous 
cavities,  and  in  these  cases  the  media  shows  more  or  less  involve- 
ment. Actual  tubercles  with  giant  cells  and  epithelioid  cells  infil- 
trate the  media;  some  of  these  go  on  to  caseation  and  others  to 
fibrosis,  and  very  often  the  inflammatory  state  causes  thrombosis 
of  the  affected  artery. 

The  multiple  miliary  nodules  which  are  seen  about  the  minute 
arteries  and  veins  of  the  meninges  in  tuberculous  meningitis  are 
not  in  the  walls  proper,  of  these  vessels,  but  have  developed  in  the 
outermost  and  loose  meshwork  of  the  adventitia. 

Some  difficulty  is  experienced  in  distinguishing  tuberculous  foci 
in  and  about  the  small  arteries.  Duerck  has  recently  demonstrated 
miliary  nodules  in  the  vessels  of  the  pia,  which  macroscopically  had 
the  appearance  of  tuberculosis,  and  yet  no  evidence  of  tuberculosis 
was  present  elsewhere  in  the  body,  while  syphilis  was  present. 

To  sum  up  the  important  points  concerning  the  productive  mes- 
arteritis,  we  have  (i)  a  type  of  inflammatory  reaction  of  the  media 
secondary  to  lesions  in  the  intima,  having  no  definite  etiological  fac- 
tor and  localized  to  the  tissues  lying  beneath  the  diseased  intima 
(Chiari's  Type  A),  and  (2)  a  mesarteritis  associated  with  inflam- 
matory infiltration  of  the  adventitia,  primary  to  intimal  prolifera- 
tion which  is  most  frequently  caused  by  syphilis  (Chiari's  type  B), 
but  which  may  also  be  induced  by  other  infections.  In  both  types 
of  productive  mesarteritis  the  newly  developed  medial  tissue,  while 
replacing  the  tissue  proper,  seldom  shows  degenerative  changes  in 
progress,  either  in  the  area  directly  affected  or  in  the  immediate 
neighborhood. 

Periarteritis  Nodosa. — There  is  a  distinct  class  of  nodular  in- 
flammatory thickening  of  the  arterial  coats  which  must  be  con- 
sidered apart  from  the  usual  inflammatory  infiltrations  of  the 
arteries. 

Up  to  the  present  there  are  about  thirty  cases  of  periarteritis 
nodosa  recorded.  The  first  description  of  the  macroscopical  ap- 
pearance was  given  by  Rokitansky  in  1852,  and  in  1866  Kussmaul 
and  Maier  gave  an  exact  histological  description  of  the  disease,  and 
its  name.     Since  these  early  reports  little  new  has  been  added  to 


Diseases  Affecting  the  Media.  37 

our  knowledge  of  the  affection,  save  to  confirm  the  early  observa- 
tions. The  later  observers  have  to  a  great  extent  confined  their 
attention  to  the  discussion  of  the  etiology  of  the  inflammatory 
process,  but  there  is  still  no  uniformity  of  opinion.  Syphilis  as  a 
factor  is  doubtful. 

Periarteritis  nodosa  is  a  disease  of  the  smaller  blood  vessels, 
more  commonly  found  in  men  than  women,  and  beginning  usually 
at  the  age  of  twenty  to  thirty  years.  The  disease  develops  as  mul- 
tiple nodules  on  the  small  arteries  or  arterioles,  and  is  most  fre- 
quently seen  on  the  coronary  artery  of  the  heart,  or  the  hepatic, 
the  mesenteric  and  the  renal  arteries.  Nevertheless,  its  distribu- 
tion may  be  very  varied  and  the  vessels  in  the  muscles,  lungs  or 
skin  are  occasionally  the  sites  of  predilection.  The  lesions  are  to 
be  seen  as  small  nodules  appearing  on  the  outside  of  the  arteries, 
sometimes  encircling  the  artery,  at  other  times  projecting  outwards 
as  a  globular  mass  the  size  of  a  pea.  At  the  bifurcation  of  a  vessel 
the  thickening  may  be  more  diffuse,  and  extend  for  half  an  inch 
or  more  along  the  artery.  The  more  distinct  enlargements  are 
found  on  vessels  lying  in  a  loose  tissue,  but  nevertheless  nodular 
thickenings  are  also  found  on  the  arteries  in  the  substance  of  the 
kidney,  spleen,  heart  and  liver. 

Remarkable  it  is  that  no  similar  disease  has  been  found  in  the 
veins,  nor  in  the  aorta  or  the  vessels  of -the  elastic  type. 

In  some  instances,  and  more  particularly  in  the  heart,  the  nodular 
thickenings  of  the  arteries  form  a  "  rosenkranzartig  "  appearances. 
There  appears  to  be  no  uniformity  in  which  the  disease  attacks  the 
arteries.  At  times  the  mesenteric  system  alone  is  affected,  at  others 
the  cutaneous  or  the  cardiac  vessels.  Consequently  the  symptoms 
vary  widely  and  the  diagnosis  is  difficult  to  make  during  life. 
With  involvement  of  the  gastro-intestinal  tract,  symptoms  of  pain 
and  diarrhoea  are  not  unusual  features.  When  the  vessels  of  the 
heart  are  affected,  and  more  particularly  when  the  intima  of  the 
arteries  has  taken  part  in  the  nodular  thickening,  symptoms  of 
angina,  or  of  myocardial  fibrosis  or  softening,  may  arise.  Very 
rarely  do  the  arteries  of  the  meninges  become  involved  in  this 
disease. 

Kussmaul  found  the  arteries  of  the  bladder,  as  well  as  those  of 


38  Arteriosclerosis.    Diseases  of  the  Media. 

the  breast  and  skin,  showing  nodular  thickenings  of  their  coats. 
Graf  found  the  same  changes  in  the  arteries  of  the  adrenals,  while 
Fletcher  described  a  type  of  periarteritis  nodosa  in  the  vasa  vas- 
orum  of  the  aorta. 

Considering  the  wide  distribution  of  the  disease  throughout  the 
body,  it  is  not  a  little  remarkable  that  the  vessels  of  the  brain  are 
seldom  if  ever  attacked,  though  Chvostek  and  Weichselbaum  and 
also  Muller  have  each  described  cases  in  which  nodules  were  present 
on  the  cerebral  arteries.  The  aorta  and  pulmonary  artery  remain 
fairly  immune. 

Of  the  individual  lesions  in  the  arteries  two  types  have  been 
described,  (i)  the  solid  nodular,  and  (2)  the  nodular  with  aneu- 
rysms. These  types  have  received  recognition  rather  from  the 
appearance  than  from  the  mode  of  origin.  Both  of  the  types 
have  had  the  same  conditions  leading  up  to  their  development,  but 
in  the  case  of  the  multiple  aneurysms,  the  reparative  tissue  about 
the  nodules  has  not  kept  pace  with  the  disturbance  in  the  media  and 
adventitia,  with  the  result  that  the  normal  blood  pressure  could  not 
be  sustained.  In  short,  the  development  of  aneurysms  is  but  a 
stage  or  a  sequel  to  the  disease  in  general. 

There  is  still  some  diversity  of  opinion  as  to  the  pathology  of 
the  nodules.  Kussmaul  and  Maier,  who  first  described  the  histol- 
ogy of  the  lesions,  and  the  majority  of  the  observers  (Muller, 
Veszpremi  and  Jansco,  Freund,  Grafared,  Longcope)  are  of  the 
opinion  that  the  lesion  is  essentially  an  inflammation,  beginning  in 
the  adventitia.  In  the  early  stages  a  round-celled  infiltration  is 
found  along  the  adventitial  vessels,  which  spreads  both  into  the 
adjoining  tissues  and  into  the  media.  Lymphocytes  are  present  in 
great  numbers  and  fibroblasts  accompany  the  tissue  infiltration. 
With  the  advance  into  the  media  the  muscle  fibres  are  pushed  aside 
and  to  a  great  extent  destroyed.  The  elastic  fibres,  later,  also 
undergo  destruction,  and  with  this  weakened  arterial  wall,  aneu- 
rysms may  be  developed.  The  thickening  of  the  intima  which  may 
develop  to  such  an  extent  as  to  occlude  the  artery,  is  looked  upon  as 
aTsecondary  process.  The  irritation  of  the  noxious  agent  in  the 
media  affords  the  stimulus  for  tissue  proliferation  in  the  intima. 


Diseases  Affecting  the  Media.  39 

Later,  secondary  degenerative  changes  may  occur  in  this  thickened 
intima. 

A  few  (Fletcher,  v.  Kahlden  and  Chvostek  and  Weichselbaum) 
held  the  view  that  the  disease  arises  in  the  intima  and  advances 
from  here  into  the  media  and  adventitia.  The  evidence  which 
these  authors  bring  forward  in  support  of  this  contention  is  not 
clear. 

Eppinger  on  the  other  hand  believed  that  the  disease  was  an 
unusual  condition  of  congenital  weakness  of  the  arterial  wall, 
which  in  consequence  to  the  rupture  of  the  elastic  lamellae  devel- 
oped multiple  aneurysms.  The  firm  nodules,  he  believed,  repre- 
sented organized  thrombi  filling  the  aneurysms  and  had  no  direct 
association  with  an  inflammatory  process  in  the  adventitia. 

Ferrari,  Meyer  and  Moenckeberg  were  of  the  opinion  that 
prior  to  any  inflammation  in  the  adventitia  or  media,  a  focal  de- 
generation of  the  muscle  elements  of  the  media  was  to  be  seen. 
Preceding  the  destructive  changes,  a  peculiar  oedematous  infiltration 
between  the  muscle  cells  was  found,  which  was  later  also  present 
in  the  adventitia.  This  focal  necrosis  of  the  media  may  later  be 
followed  by  an  inflammatory  reaction,  or  by  aneurysmal  dilatation 
which  in  the  advanced  condition  develops  a  secondary  proliferation 
of  the  adventitia. 

As  a  causative  factor  in  periarteritis  nodosa,  syphilis  has  been 
spoken  by  Kussmaul,  Chvostek  and  Weichselbaum  and  Graf.  But 
in  only  a  few  instances  has  syphilis  been  shown  to  have  been  present 
elsewhere  in  the  body.  Although  it  must  be  recognized,  from  the 
description  here  given,  that  the  lesions  are  of  the  same  order  as 
those  encountered  in  syphilitic  mesarteritis,  nevertheless  the  weight 
of  evidence  is  against  the  specific  nature  of  the  disorder.  Various 
bacterial  organisms  have  been  found  in  the  lesions  (Graf  and  Bom- 
bard), but  no  single  infection  can  be  associated  with  the  disease. 
One  must,  however,  agree  with  Longecope  that  in  spite  of  the 
failure  to  associate  the  lesions  with  a  particular  kind  of  organism, 
there  are  many  features  in  the  disease  which  suggest  an  acute 
infection. 


40  Arteriosclerosis.    Diseases  of  the  Media. 

Degenerative  Lesions. 

V\'t  now  come  to  the  second  class  of  medial  diseases,  that  in  which 
the  process  of  degeneration  is  much  more  pronounced  than  the 
active  repair  of  the  tissues.  In  some  types  and  instances,  repair  is 
entirely  wanting,  while  in  others  an  attempt  is  made  to  replace  the 
degenerated  areas  by  fibrous  tissue.  Hence  this  type  of  degenera- 
tive lesions  does  not  only  include  those  cases  showing  pure  tissue 
destruction,  but  also  those  in  Avhich  the  primary  and  extensive  tissue 
destruction  has  called  forth  some  production  of  new  tissue. 

Atrophy. — Similar  to  atrophic  changes  in  the  various  tissues  of 
the  body,  a  process  of  atrophy  may  occur  in  the  walls  of  the  arteries. 
This  atrophic  change  is  found  in  the  arteries  of  the  various  types 
and  affects  mainly  the  media. 

Under  some  conditions  atrophy  of  the  arterial  coats  occurs  as  a 
physiological  process.  In  instances  Avhere  an  artery  suffers  disuse 
the  more  specialized  tissues  in  the  Avail  diminish  in  size  and  even- 
tually disappear.  At  birth  when  the  pressure  relation  of  the  blood 
in  the  pulmonary  arter\-  and  the  aorta  are  altered,  the  ductus 
arteriosus  by  its  muscular  walls  closes  the  lumen  of  the  vessel. 
Thrombi  occur  only  in  unusual  cases  during  the  closure  of  the 
ductus.  The  intima,  however,  rapidly  closes  the  potential  lumen 
and  obliterates  the  blood  channel  by  a  connective  tissue  prolifera- 
tion. Gradually  then,  the  muscle  elements  of  the  media  diminish 
in  size  and  number,  until  they  have  entirely  disappeared  and  their 
place  is  taken  by  fibrous  tissue. 

A  similar  atrophy  may  be  observed  in  the  walls  of  a  thrombosed 
arter}',  although  the  loss  of  the  tissue  is  more  gradual.  In  each  of 
these  instances  the  factor  of  disuse  is  coupled  with  an  alteration  of 
nutrition  which  plays  an  important  part  in  the  process.  Particu- 
larly in  an  adult  vessel  the  sudden  shutting  oft"  of  nutrition,  by 
thrombosis,  from  the  lumen  acts  deleteriously  upon  the  tissues  of 
the  inner  zone  of  the  artery  opposite  the  thrombus. 

In  old  age,  it  is  most  common  to  find  atrophic  conditions  asso- 
ciated directly  with  the  altered  nutrition  of  senility.  At  the  same 
time  in  which  an  atroph}-  or  decrease  in  amount  is  taking  place  of 
one  tissue,  there  is  commonly  an  increase  in  the  tissues  of  a  lower 
order.     This  atrophy  of  certain  tissues  is  an  indication  of  the  wear 


Diseases  Affecting  the  Media.  41 

and  tear  which  is  taking  place  from  the  constant  activity  of  the  part. 
Consequent  to  the  loss  of  the  tissue  cells  of  a  higher  order,  there  is 
a  relative — or  at  times  an  actual  sclerosis.  In  the  arteries,  Aschoff 
speaks  of  this  as  an  "  Abnutzungssclerose  " — wear  and  tear  sclerosis. 
This  we  believe  is  a  very  happy  expression  for  the  condition. 

Marchand  has  laid  stress  upon  the  close  association  of  nutritional 
changes  with  the  process  of  arteriosclerosis.  While  this  explana- 
tion is  very  apt  for  the  scleroses  of  old  age,  we  feel  that  there  must 
be  some  further  underlying  cause  in  the  numerous  arterial  scleroses 
occurring  in  early  adult  life.  However,  this  is  aside  from  our  main 
point. 

In  actual  atrophies  of  old  age  similar  changes  occur  in  the  muscle 
fibres,  as  are  seen  in  the  involuntary  muscle  cells  elsewhere.  The 
individual  fibres  become  smaller  and  narrower,  the  nucleus  appears 
granular  and  has  a  rough  outline.  About  the  nucleus,  and  parties 
larly  at  the  poles,  there  is  a  fine  deposit  of  granular  fat  or  lipoid 
bodies  which  form  a  wedge-shaped  cluster.  These  granules  stain 
readily  with  Sudan  III,  but  with  Nile  blue  sulphate  are  colored 
blue,  indicating  according  to  Lorrain  Smith  the  presence  of  free  (or 
possibly  loosely  combined)  fatty  acids. 

By  the  actual  measurement  of  a  large  series  of  specimens,  Kani 
has  recently  shown  that  the  aorta  continues  to  increase  in  thickness 
up  to  the  age  of  fifty.  This  he  considered  a  physiological  process. 
From  this  time  on  however,  the  vessels  were  again  diminished  in 
thickness. 

These  results  are  in  agreement  with  our  own  observations  in 
which  we  found  that  the  atrophic  change  to  be  seen  under  the 
microscope  began  at  about  the  fiftieth  year.  These  observations 
are  more  fully  discussed  in  our  section  upon  Senile  Arteriosclerosis. 

With  this  process  of  atrophy  and  degeneration  of  the  muscle 
fibres,  the  blood  pressure  within  the  artery  crowds  the  elastic 
lamellse  closer  together,  and  leads  to  a  slight — and  in  actual  meas- 
urement, imperceptible  dilatation  of  the  artery.  Practically,  every 
artery  of  the  elastic  type  shows  after  the  age  of  fifty  a  crowding 
together  of  the  concentric  elastic  layers.  At  the  same  time,  while 
there  is  a  relative  increase  in  the  elastic  tissue  of  the  media,  there 
is  also  an  actual  increase  of  elastic  fibres,  due  in  part  to  a  splitting 


42  Arteriosclerosis.    Diseases  of  the  Media. 

and  feathering  of  the  elastic  strands,  and  also  due  to  the  production 
of  new  fibres  and  fibrils  in  the  place  of  the  muscle  tissue  lost. 

Following  the  slow  process  of  muscular  degeneration  the  sites  of 
the  lipiod  bodies  become  occupied  by  a  calcareous  deposit,  and 
similar  wedge-shaped  aggregations  of  calcareous  salts  are  to  be 
found  between  the  elastic  fibres.  When  such  a  deposit  is  present, 
the  muscle  fibres  have  been  destroyed.  This  necrobiotic  process  we 
shall  discuss  again. 

Simple  diffuse  atrophy  of  the  media  of  the  arteries  of  the  mus- 
cular type  is  not  so  commonly  recognized.  The  process  is,  never- 
theless, just  as  common  as  in  the  vessels  of  the  elastic  type,  but  as 
the  process  is  decidedly  progressive,  severe  degenerative  changes 
are  soon  under  way.  In  the  iliac,  femoral  and  radial  arteries, 
besides  the  larger  abdominal  arteries,  there  are  not  infrequently 
atrophic  changes  present  in  the  muscular  coat.  The  muscle  cells 
become  smaller,  the  nuclei  granular,  and  the  longitudinal  striae 
appear  more  prominently.  The  vessel  wall  becomes  actually  thinner, 
and  as  the  process  of  atrophy  progresses  unequally  along  the  vessel, 
there  are  small  pouchings  produced  in  the  wall.  As,  however,  the 
muscular  coat  of  these  vessels  is  not  possessed  of  concentric  elastic 
bands,  there  is  no  reparative  tissue  to  substitute  for  the  degenerated 
muscle  elements,  and  hence  when  once  started  the  simple  atrophy 
passes  into  different  stages  of  severe  degeneration.  Occasionally 
there  is  an  attempt  at  the  development  of  new  elastic  fibrils,  but 
never  are  these  produced  in  sufficient  cjuantity  to  protect  the  artery 
from  the  later  stages  of  degeneration. 

Sohma  recognized  in  the  arteries  of  the  ovary,  an  atrophy  of  the 
muscle  cells  in  the  media,  occurring  in  the  vessels  passing  to  the 
matured  Graffian  follicles.  He  believed  that  this  process  resulted 
from  disuse,  following  the  extrusion  of  the  ovum  of  that  particular 
follicle  when  the  requirements  of  the  follicle  were  diminished. 
Similar  processes  have  also  been  observed  in  the  arteries  of  the 
uterus  following  menstruation  (Pankow). 

It  was  long  ago  pointed  out  by  Virchow  and  subsequently  verified 
by  others,  that  chronic  wasting  disease,  and  also  chlorosis  was  asso- 
ciated with  a  true  atrophy  of  the  vessel  walls.  Not  alone  is  the 
arterial  wall  thinned,  but  in  these  cases,  he  says,  the  lumen  of  the 


Diseases  Affecting  the  Media.  43 

vessel  is  itself  narrowed.  Apparently  the  blood  is  diminished  in 
quantity  and  is  lowered  in  its  efficiency  of  maintaining  proper  nutri- 
tion. Simple  atrophy  also  occurs  in  the  arterial  stumps  of  ampu- 
tated limbs. 

Localized  areas  of  medial  atrophy  are  quite  commonly  met  with 
both  in  the  vessels  of  the  elastic  type  and  those  of  the  muscular 
type.  Thoma,  in  pointing  out  that  a  weakening  of  the  media  pre- 
cedes the  development  of  an  intimal  arteriosclerosis,  admits  that  at 
times  the  order  is  reversed.  In  my  own  opinion,  the  latter  process, 
i.  e.,  the  primary  development  of  an  intimal  sclerosis  with  plaque- 
like thickening  followed  by  a  pressure  atrophy  of  the  media,  is  far 
more  common  than  the  former.  We  have  every  evidence  in  support 
of  this  statement.  On  the  one  hand,  there  is  in  the  early  stages  of 
endarteritis  nodosa  (leaving  aside  the  syphilitic)  no  macroscopical 
or  histological  evidence  of  weakening  or  disease  in  the  media,  and  it 
is  only  with  the  progressive  thickening  and  degenerative  changes  in 
the  intima  that  the  media  gives  any  evidence  of  change.  In  some 
instances  this  medial  change  is  not  truly  degenerative — of  the  nature 
of  fatty,  hyaline  or  calcareous  invasion — but  the  effect  of  focal 
nodular  pressure  is  shown  in  a  narrowing  of  the  media  at  one  point. 
The  muscle  fibres  become  crowded  together,  and  in  themselves  are 
narrowed;  the  elastic  fibres  too  are  more  compactly  arranged.  In 
short  the  normal  tissues  of  the  media  must  accommodate  themselves 
to  a  nodular  overgrowth  in  the  intima,  which  develops  not  alone 
inwards  into  the  lumen  of  the  vessel,  but  also  outwards  into  the 
substance  of  the  media.  In  these  circumstances  the  medial  fibres 
which  are  stretched  over  the  intimal  nodule,  no  longed  possess  the 
same  freedom  of  action  of  expansion  and  contraction.  It  is  on 
account  of  this  inability  of  free  movement  that  when  further  degen- 
erative changes  occur  in  the  affected  media,  and  more  particularly 
when  the  process  of  calcification  results,  that  the  tissue  elements 
become  fixed  in  the  extended  position. 

It  is  quite  obvious  that  the  function  of  atrophied  arteries  is  much 
diminished  particularly  as  the  most  active  tissue  in  the  media,  the 
muscle,  is  the  first  to  undergo  atrophy.  There  is  a  decided  decrease 
in  the  elasticity  of  these  vessels,  consequent  to  which  there  are  the 
nutritional  sequelae  in  other  tissues  and  organs  of  the  body. 


44  Arteriosclerosis.    Diseases  of  the  Media. 

Necrosis. — Necrosis  of  the  arterial  wall  is  an  unusual  feature 
save  when  associated  with  acute  infections.  These  acute  infective 
necroses  are  commonly  associated  with  an  intense  cellular  infiltra- 
tion and  even  pus  formation,  so  that  small  abscesses  are  formed  in 
the  arterial  wall.  Such  conditions  are  more  properly  discussed 
under  Acute  Mesarteritis.  The  infection  in  these  cases  reaches  the 
arterial  coat  by  the  vasa  vasorum  about  which  processes  of  varying 
severity  develop  depending  upon  the  nature  of  the  infecting  agent. 

Necroses  not  associated  with  infection  may  occur  in  the  artery 
through  the  occlusion  of  some  of  the  nutrient  vessels.  Nevertheless, 
it  is  surprising  that  when  an  artery  is  dissected  from  its  surrounding 
tissues,  necrosis  does  not  take  place  in  the  arterial  wall  proper. 

From  what  we  have  been  able  to  observe,  it  appears  that  the  dis- 
turbance of  the  nutrient  vessels,  as  they  lie  in  the  adventitia,  does  not 
severely  effect  the  health  of  the  artery.  On  the  other  hand,  there 
appears  to  be  a  system  of  vasa  vasorum  which  do  not  come  from  the 
adventitial  vessels  but  arise  from  the  smaller  arterioles  as  they  take 
their  origin  from  the  main  artery  and  pass  through  the  media.  In 
two  instances,  both  being  cases  of  scarlet  fever,  we  have  observed 
the  occlusion  by  thrombus  of  the  vasa  in  the  media  with  a  non-infec- 
tious destruction  of  the  middle  coat  of  the  aorta. 

Fischer  applied  the  term  "arterionecrosis"  to  the  degenerative 
lesion  occurring  in  experimental  adrenaln  arteriosclerosis.  He  be- 
lieved that  the  tissue  destruction  of  the  media  was  a  process  of 
rapid  necrosis  in  which  a  final  stage  of  calcification  occurred. 
Shortly  following  his  publication,  we  were  able  to  demonstrate  in  his 
own  specimens  a  process  of  fatty  degeneration  which  precedes  the 
final  stage  of  calcification. 

It  is  a  point  of  very  fine  differentiation  to  distinguish  between  the 
rapid  process  of  fatty  degeneration  with  calcification  and  true  necro- 
sis, i.  e.,  between  necrobiosis  and  necrosis.  Curious  it  is,  that  these 
experimental  lesions  in  the  rabbit  are  so  prone  to  become  calcificied. 
It  is  probable  that  the  relatively  high  calcium  content  of  this  ani- 
mal's blood  has  something  to  do  with  the  rapidity  in  which  the 
arterial  changes  occur.  However,  as  definite  and  successive  stages 
can  be  demonstrated  in  the  process  of  destruction  of  the  arterial 
cells  in  these  animals  we  distinguish  this  type  of  disease  from  true 
necrosis. 


Diseases  Affecting  the  Media.  45 

Fatty  Degeneration. — In  the  vessels  both  of  the  muscular  type 
and  the  elastic  type,  one  of  the  milder  forms  of  degeneration  is  the 
granular  fatty  degeneration  of  the  muscular  fibres.  In  this  there  is 
found  a  deposition  of  fine  granular  fat  droplets  arranged  in  wedge- 
shaped  masses  about  the  nucleus.  The  nucleus  itself  does  not  show 
any  change  in  its  structure,  nor  does  the  muscle  fibre  appear  altered 
in  its  size  or  shape.  The  fine  fat  granules  are  the  only  evidence 
which  we  can  find  of  medial  disease.  These  early  degenerations  do 
not  impair  to  any  extent  the  usefulness  of  the  artery,  and  when  the 
causative  agent  is  removed  and  proper  nutrition  again  supplied  to 
the  media,  it  wholly  recovers  itself  and  the  fat  disappears  from  the 
cell.  The  connective  tissue  cells  are  not  altered  or  stimulated  to 
growth  nor  are  any  changes  to  be  noted  in  the  elastic  fibres. 

When,  however,  the  condition  becomes  more  advanced  we  find 
that  the  fatty  degeneration  is  isolated  to  patches  of  the  vessel,  and 
seldom  is  the  entire  circumference  involved  in  the  process.  These 
patches  are  found  to  lie  away  from  the  vasa  vasorum.  Close  exami- 
nation shows  that  the  muscle  fibres  are  in  all  stages  of  fatty  degen- 
eration— from  the  fine  sprinkling  of  fat  in  the  protoplasm  to  the 
coarst  fat  droplets  occupying  almost  the  entire  cell  body — and  the 
nucleus  is  found  much  fragmented.  Later  the  complete  disintegra- 
tion of  the  muscle  cells  is  also  observed  in  which  case  the  fat  drop- 
lets lie  free  and  between  the  neighboring  muscle  strands.  When  a 
number  of  muscle  fibres  have  become  disintegrated  and  have  liber- 
ated their  fat  in  this  manner,  we  have  a  condition  in  the  media 
resembling  atheroma.  Such  localized  areas  of  fatty  degeneration 
may  have  an  excessive  amount  of  connective  tissue  developed  about 
them. 

When  this  process  is  present  in  the  arteries  of  the  elastic  type, 
the  elastic  strands  become  pressed  together  from  the  force  of  the 
normal  blood  pressure  within  the  artery.  Necessarily  then  the 
artery  becomes  thinned  at  this  point.  If  the  elastic  fibres  are  also 
involved  in  the  degenerative  process,  the  possibility  of  the  vessel 
yielding  and  forming  an  aneurysm  at  this  site  is  very  great.  The 
elastic  fibres  when  they  have  lost  their  normal  elastic  power  can  only 
yield  to  and  not  repel  the  pressure  bearing  on  them.  Thoma  be- 
lieved that  at  this  stage,  when  the  media  was  thinned  and  weakened, 


46  Arteriosclerosis.    Diseases  of  the  Media. 

the  intima  compensated  for  the  loss  of  strength  and  enlarged  lumen 
of  the  vessel,  by  the  proliferation  of  its  superficial  layer. 

Such  localized  and  irregular  patches  of  fatty  degeneration  in  the 
media  occur  most  frequently  in  the  vessels  of  the  extremities,  and 
it  is  remarkable  with  what  rapidity  such  lesions  develop.  Areas  of 
sufficient  size  to  be  seen  macroscopically  are  not  infrequent  in  the 
femoral  arteries.  Microscopically,  these  areas  present  masses  of  fat 
granules,  interwoven  with  a  few  elastic  fibres  and  some  partially 
preserved  muscle  cells. 

Where  this  process  of  fatty  degeneration  is  advanced  I  have 
found  the  presence  of  cholesterin  crystals  and  fatty  acids,  both 
free  and  combined  in  the  media  as  well  as  in  the  intima. 

It  is  indeed  common  to  observe  these  lesser  grades  of  fatty  de- 
generation in  the  media  of  most  arteries  of  the  body.  However,  the 
small  peripheral  vessels  show  the  condition  less  frequently  than  it  is 
obtained  in  the  aorta  and  its  main  branches.  Nevertheless,  it  is  un- 
usual to  have  this  process  of  fatty  degeneration  advance  to  actual 
atheroma,  as  soon  in  the  intima.  In  the  intima,  the  degenerative 
changes  take  place  in  its  deepest  layer,  the  musculo-elastic  lamella, 
where  there  are  no  nourishing  capillaries.  The  areas  of  degenera- 
tion in  the  intima  are  almost  always  accompanied  by  proliferative 
changes  in  the  endothelium  and  subendothelial  connective  tissue, 
which  still  further  cut  off  the  nutrient  supply  from  the  vessel  lumen, 
with  the  result  that  the  atheromatous  plaque  becomes  progressively 
larger.  In  the  media,  the  fatty  changes  begin  in  small  foci  away 
from  the  vasa  vasorum,  but  sufficient  nourishment  is  obtained  to 
maintain  the  life  of  the  cells  so  that  complete  destruction  does  not 
occur.  This  does  not  hold,  however,  for  the  iliac,  femoral,  radial 
and  other  larger  peripheral  arteries,  where  complete  destruction  of 
the  involved  cells  does  take  place,  and  a  fatty  calcareous  plaque  simi- 
lar to  intimal  lesions  is  produced  in  the  media. 

Occasionally  too  it  is  noted,  and  this  particularly  in  the  aorta,  that 
a  fatty  degeneration  of  the  musculo-elastic  layer  of  the  intima  will 
advance  into  the  inner  layers  of  the  media.  In  these  cases  the  fatty 
change  may  be  quite  severe, — particularly  when  the  intimal  disease 
has  become  an  atheromatous  ulcer.  In  these  cases  it  is  usually 
found  that  some  connective  strands  have  developed  in  the  neighbor- 


Diseases  Affecting  the  Media.  47 

hood  of  the  ulcer,  the  base  of  which  rests  on  the  media.  The 
muscle  cells  of  the  media,  near  the  ulcer  show  extensive  destruction 
and  fatty  degeneration,  while  the  elastic  fibres  present  hyaline  and 
fatty  degeneration.  Apparent  ruptured  elastic  fibres  are  frequent, 
but  true  ruptured  fibres  do  not  occur.  The  apparent  ruptures  pres- 
ent this  appearance  on  account  of  the  isolated  degenerations  in  the 
strands  which  do  not  permit  the  normal  elastic-fibre  staining. 

Weiszmann  and  Neumann,  Manchot  and  others  have  noted  that 
in  areas  undergoing  fatty  degeneration,  the  elastic  fibres  are  fre- 
quently associated  in  this  process,  so  that  in  the  later  stages  these 
fibres  undergo  a  partial  dissolution  leaving  nothing  but  the  fine 
granular  fat  particles  along  their  course.  Eberhardt  regarded  these 
granular  degenerations  as  artifacts  but  the  later  studies  of  Dmitri- 
jeff  and  Jores  have  shown  definitely  the  various  stages  of  a  fatty 
degeneration  in  these  fibres. 

According  to  Dmitrijeff,  the  degenerations  in  the  elastic  fibres  of 
the  media  are  the  earliest  signs  of  lesions  in  this  coat,  and  are 
also  to  be  recognized  more  particularly  in  the  inner  zone,  and  later 
also  in  the  middle  and  outer  zone  of  the  vessel  wall.  He  believes 
that  there  is  a  definite  change  in  the  chemical  composition  of  these 
fibres  in  the  process  of  degeneration. 

That  .the  elastic  fibres  do  undergo  a  fatty  change  is  not  to  be 
denied,  but  there  is  still  a  considerable  controversy  in  what  manner 
this  fatty  metamorphosis  is  brought  about.  Jores  has  found  defi- 
nite fatty  degenerated  elastic  fibres,  and  I  have  noted  this  condition 
not  infrequently  in  the  internal  elastic  lamina  and  the  elastic  lamella 
of  the  aorta,  and  in  experimental  arteriosclerosis  of  animals  the  proc- 
ess is  common  when  sought  for.  When  the  elastic  fibres  show  fatty 
degeneration,  they  lose  their  affinity  for  elastin  stains,  becoming 
only  a  pinkish  color  with  Weigert's  stain.  With  fuchselin  the  fine 
fat  droplets  are  seen  to  crowd  the  elastic  fibres  at  the  degenerated 
areas.  It  is  generally  held  that  the  elastic  fibres  are  non-nucleated 
structures,  without  individual  powers  of  reproduction  or  of  carrying 
on  functional  metabolism.  On  this  ground,  it  is  claimed  by  some 
that  since  evidence  is  lacking  that  proteid  bodies  can  be  converted 
into  fat,  and  all  fatty  degeneration  must  be  of  the  nature  of  lowered 
cell  vitality  with  accumulation  of  absorbed  fat,  it  is  impossible  to 


48  Arteriosclerosis.    Diseases  of  the  Media. 

recognize  a  fatty  degeneration  of  the  elastic  fibres.  These  authors 
believe  that  the  fat  noted  in  association  with  the  elastic  strands 
is  to  be  found  not  in  the  fibres,  but  adhering  to  their  external  sur- 
face. On  the  other  hand,  it  is  shown  by  others  that  a  fat  accumula- 
tion may  take  place  in  the  form  of  fine  granules  within  the  fibres. 
These  authors  accept  the  non-vital  nature  of  the  elastic  strands,  but 
point  out  that  some  substance  within  the  fibres  when  altered  or 
decomposed  has  a  strong  attraction  for  fatty  substances.  These 
degenerated  elastic  strands  are  often  to  be  found  in  the  focal  patches' 
of  fatty  change  of  the  muscle  cells. 

The  diffuse  uniform  fatty  degeneration  as  is  so  commonly  en- 
countered in  the  aorta  is  usually  associated  with  conditions  of 
altered  nutrition,  or  with  toxaemias.  Old  age  is  a  common  factor 
in  the  mild  t3^pe  of  the  lesion,  and  the  amount  of  fat  present  in  the 
tissue  of  the  media  increases  with  advancing  years  over  fifty-five. 
The  lesion  is  a  truly  degenerative  one,  but  it  rarely  leads  to  serious 
conditions.  Even  in  such  vessels  of  the  aged,  which  from  macro- 
scopic appearance  are  sound  and  healthy,  and  which  show  no  evi- 
dence of  the  common  scleroses  in  the  intima,  the  microscopic  exami- 
nation of  the  media  shows  diffuse  fatty  and  calcareous  degenera- 
tions of  the  muscle  elements.  The  elastic  fibres  are  rarely  involved 
in  this  disease,  save  when  other  unrelated  lesions  are  also  present  in 
the  vessel. 

In  younger  individuals  toxsemias  of  various  kinds  lead  to  fatty 
degeneration  of  the  muscle  cells  from  which  they  may  recover 
themselves.  These  degenerations  differ  from  the  senile  type  in 
showing  fatty  changes  without  the  calcareous  depositions,  and 
further  in  showing  a  less  amount  of  destruction  or  loss  in  the 
muscle  fibres.  Whereas  in  the  senile  medial  arteriosclerosis,  the 
elastic  fibres  become  irregular  and  show  a  splitting  of  the  coarser 
strands  along  with  the  development  of  a  meshwork  of  cross  fibres, 
the  toxjemic  degenerations  show  little  or  no  change  in  the  elastic 
fibres  and  no  crowding  of  the  elastic  lamellse.  Severe  diphtheria 
leads  to  such  a  fatty  degeneration,  while  more  rarely  eclampsia, 
tvphoid,  scarlet  and  other  fevers  have  the  same  effect. 

It  is  also  to  be  noted  that  long-continued  strain  upon  the  arterial 
wall,  such  as  is  brought  about  by  a  continued  or  intermittent  high 


Diseases  Affecting  the  Media.  49 

blood  pressure  has  a  deteriorating  effect  upon  the  muscle  fibres  of 
the  media  which  although  not  to  be  distinguished  in  its  early  stages 
macroscopically,  is  nevertheless  readily  recognizable  under  the 
microscope.  The  effect  of  continued  strain  is,  I  believe,  primarily 
functional  exhaustion  of  the  muscle  cells  and  having  this  mechan- 
ical irritant  continued  upon  the  exhausted  cells  leads  to  organic 
alterations  within  the  cells.  These  degenerations  are  most  easily 
demonstrated  in  the  fat  granules  which  accumulate  in  the  muscle 
fibres.  Other  cellular  changes  are  also  present  but  less  easily  dem- 
onstrated with  accuracy. 

In  the  human  subject  it  is  with  some  uncertainty  that  degenera- 
tive lesions  in  the  arteries  can  be  ascribed  to  strain,  overwork,  or 
functional  exhaustion.  In  experimental  animals,  this  can  be  con- 
trolled. In  selecting  young  animals  of  good  stock  and  in  healthy 
condition,  one  may  exclude  to  a  very  low  percentage  spontaneous 
arterial  disease,  or  lesions  arising  from  causes  other  than  those 
directly  under  the  control  of  the  operator.  Further  when  proper 
controls  of  sufficient  number  are  examined  in  conjunction  with 
those  experimented  upon,  the  possible  error  arising  from  unlooked 
for  causes  is  reduced  to  a  minimum. 

It  has  been  previously  shown  (Harvey,  Klotz)  that  when  the 
arteries  in  animals  are  subjected  to  increased  tension  by  mechanical 
means,  degenerative  changes  are  brought  about  in  the  intima  and 
media.  The  intimal  changes  are  similar  to  those  described  by 
Jores  in  "  true  arterio-sclerosis  "  in  man.  A  primary  hypertrophy 
of  the  musculo-elastic  layer  with  a  splitting  of  the  internal  elastic 
lamina  is  produced,  which  is  soon  followed  by  a  fatty  degeneration 
of  the  muscle  elements.  In  all  respects  this  intimal  lesion  simulates 
arteriosclerosis  as  seen  in  the  human  aorta.  Not  only  does  the 
intima  show  diseased  changes,  but  the  media  is  also  affected.  The 
muscle  fibres  are  altered  and  undergo  fatty  and  calcareous  degener- 
ation. 

It  is  to  be  noted  that  although  both  intimal  and  medial  disease 
can  be  produced  in  the  arteries  by  purely  mechanical  means,  that 
theseJesions  develop  quite  apart  from  each  other,  and  seem  to  bear 
no  direct  relation  in  their  process  of  development.  At  the  sites  of 
the  medial  degeneration,    from  the  earliest   development  to   such 


50  Arteriosclerosis.    Diseases  of  the  Media. 

lesions  leading  to  aneurysms,  there  may  be  little  or  no  change  in 
the  contiguous  intimal  tissue.  On  the  other  hand  again,  the  much 
thickened  and  atheromatous  intima  produced  in  experimental  ani- 
mals is  often  found  to  overlie  an  unaltered  media.  Here,  however, 
we  must  point  out  that  in  our  animals,  these  two  types  of  arterial 
lesions  developed  in  arteries  of  different  kinds.  The  medial  de- 
generations are  prone  to  occur  in  the  aorta  while  the  intimal  athe- 
roma was  more  pronounced  in  the  branches  (carotids)  of  this  ves- 
sel. In  studying  such  lesions  and  offering  an  explanation  for  their 
development  we  must  not  lose  sight  of  the  normal  structure  and  the 
function  of  the  artery.  In  the  branches  of  the  aorta  a  reserve 
power  is  developed  mainly  by  hyperplasia  of  the  musculo-elastic 
layer,  and  when  this  hyperplasia  has  once  taken  place  atheromatous 
changes  soon  follow  (Jores).  On  the  other  hand,  our  experiments 
of  increasing  the  pressure  in  the  thoracic  aorta,  have  so  over- 
strained the  tissues  of  the  aorta  to  allow  little  active  repair,  in 
consequence  of  which  progressive  degeneration  is  evident  in  the 
functional  and  active  tissue  of  the  media.  When  the  aorta,  how- 
ever, was  subjected  to  less  strain  an  intimal  hyperplasia  of  the  mus- 
culo-elastic layer  with  secondary  development  of  atheroma  was  also 
evident. 

The  results  of  the  experiments  along  this  line  have  been  directly 
contradictory  to  the  views  of  Thoma  on  the  nature  and  development 
of  arteriosclerosis. 

Whereas  it  is  well  established  that  an  intimal  proliferation  does 
follow  a  medial  change  of  the  nature  of  an  inflammation,  Bouchard 
claims  that  in  those  cases  lacking  the  cellular  and  inflammatory  in- 
filtration of  the  media,  the  intimal  hyperplasia  is  of  the  nature 
described  by  Winniwarter  in  endarteritis  obliterans.  This  latter 
disease  is  regarded  as  a  primary  affection  in  the  intima,  having  no 
association  with  medial  changes. 

Dmitri  Jeff  believes  that  degenerative  changes  arise  in  the  elastic 
fibres  of  the  media  in  the  earliest  stages  of  the  disease.  In  the 
event  of  an  intimal  disease  being  present,  these  degenerations  are 
first  to  be  found  in  the  innermost  layers  of  the  media,  but  later 
similar  degenerations  also  occur  in  the  middle  and  outer  zones. 
The  changes  in  the  elastic  fibres  is  mainly  one  of  staining  reaction. 


Diseases  Affecting  the  Media.  51 

which  Dmitri jeff  believes  indicates  a  chemical  change  in  the  sub- 
stance of  the  fiber. 

Such  variations  in  the  staining  of  the  elastic  fibres  often  gives  the 
appearance  of  a  rupture  of  their  continuity,  as  has  been  contended 
by  Zwingmann,  Waegner  and  others.  It  is  seldom  that  true  rup- 
ture of  these  fibers  is  to  be  found,  save  in  association  vith  ruptured 
aneurysms.  Most  frequently,  as  is  the  case  in  syphilitic  aortitis, 
the  elastic  fibres  have  in  focal  areas  entirely  lost  their  selective 
staining  powers,  and  appear  to  come  abruptly  to  an  end.  Xever- 
theless  these  fibres  have  small  unstained  strands  uniting  the  appar- 
ent broken  ends. 

Save  in  the  experimental  production  of  sei^ere  arterial  lesions, 
in  which  aneurysms  had  developed  and  in  ruptured  mycotic  aneu- 
rA'sms  I  have  never  found  undoubted  ruptured  elastic,  fibres.  In 
human  arteriosclerosis,  where  by  the  use  of  Weigert's  elastin  stain 
alone,  there  appeared  many  apparent  ruptured  elastic  fibres,  many 
of  which  exhibited  .the  characteristic  brush-like  end,  I  have  been 
able  to  demonstrate  the  intervening  degenerated  segment  containing 
either  fat  or  a  hyaline  substance.  The  fibrillation  of  the  so-called 
ruptured  elastic  fibre  is  a  process  more  of  less  common  to  all  de- 
generating elastic  tissue. 

With  our  present  knowledge  of  the  nature  of  elastic  fibres  it  is 
difficult  to  say  what  is  the  fate  of  degenerating  elastic  tissue.  Al- 
though we  are  aware  of  the  deposition  of  fatty  granules,  of  calcar- 
eous salts  and  of  a  hyaline  change  in  the  elastic  fibres,  we  cannot 
trace  the  steps  in  the  process  of  the  gradual  melting  away  and  dis- 
appearance of  this  tissue. 

Calcareous  Degeneration. — Closely  associated  with  the  deposit 
of  fat  in  the  arterial  wall,  whether  in  the  intima  or  in  the  media,  is 
the  calcareous  degeneration. 

Some  years  ago  we  brought  forward  evidence  of  the  direct 
chemical  relation  between  the  primary  fatty  degeneration  and  the 
deposit  of  calcium  salts  in  the  tissues.  Certain  features  of  this 
contention  were  opposed,  but  we  believe  on  insecure  grounds.  As 
in  all  degenerative  processes,  there  are  varying  stages  of  the  con- 
dition until  the  fully  matured  chemical  reaction  has  taken  place. 
So,  too,  in  the  process  of  fatty  degeneration,  and  particularly  as 


62  Arteriosclerosis.    Diseases  of  the  Media. 

the  meaning  of  this  term  is  to  be  observed  today,  a  lowered  vitaHty 
of  the  cell  with  an  accumulation  of  fat  products, — there  are  all 
stages  of  fat  accumulation,  first  taking  place  in  a  partly  damaged 
cell,  and  if  the  process  is  continuous,  increasing  until  the  life  of  the 
cell  is  so  damaged  that  it  can  no  longer  attract  materials  to  it. 
When  a  cell  has  reached  this  low  ebb  of  its  life  processes,  it  usually 
goes  on  to  complete  destruction,  liberating  its  stored  up  contents. 
It  is  this  liberated  fat  which  is  acted  upon  by  the  tissue  enzymes 
and  gives  rise  to  free  fatty  acids,  which  attract  calcium  salts.  It 
is  probable  that  at  no  stage  in  the  process  of  fatty  degeneration,  and 
while  the  fat  is  still  within  living  cells,  do  calcium  salts  enter  a 
reaction  with  the  fatty  substances.  Hence  in  such  tissues  where 
the  fat  is  still  contained  within  living  cells,  no  excess  of  calcium  is 
to  be  found.  On  the  other  hand  also,  as  we  have  previously  pointed 
out,  the  chemical  changes  are  not  complete  when  the  calcium  is 
precipitated  by  the  fatty  acids.  A  succeeding  stage  is  found  in 
which  double  salts  of  calcium  with  fatty  acids  and  carbonates  or 
phosphates  are  found,  and  in  this  condition  no  difficulty  is  obtained 
in  demonstrating  the  presence  of  calcium,  fatty  acids  and  carbon- 
ates or  phosphates  in  the  same  material.  If,  however,  a  still  later 
stage  is  examined,  it  will  be  found  that  the  fatty  acid  portion  has 
been  entirely  replaced  by  the  phosphatic  and  carbonic  acid  radicals, 
and  as  Wells  has  pointed  out,  the  phosphates  and  carbonates  of 
calcium  exist  in  these  masses  in  about  the  same  proportion  as  in 
bone. 

Whether  the  calcareous  degeneration  occurs  in  the  intima  or  in 
the  media,  it  is  found  that  the  nature  of  the  process  is  the  same. 

However,  although  the  stages  of  the  calcareous  degeneration  of 
the  arteries  are  the  same  for  those  of  the  muscular  and  of  the 
elastic  type,  the  histological  picture  of  the  deposition  of  calcium 
salts  differs  somewhat  in  these. 

The  clinician  constantly  meets  with  arteriosclerosis  in  the  ves- 
sels of  the  extremities  and  not  infrequently  is  confronted  with 
grave  disturbances  of  nutrition  as  sequelae.  These  vessels  of  the 
muscular  type  become  rigid  and  inelastic  and  are  unable  to  properly 
control  the  blood  supply  of  the  part.  Thromboses,  with  resulting 
gangrene,    are   the   dreaded   outcome   of   these   diseased    arteries. 


Diseases  Affecting  the  Media.  53 

Similar  lesions  to  those  present  in  the  palpable  arteries  also  develop 
in  the  vessels  of  the  internal  organs  (uterus,  spleen,  thyroid  and 
mesenteric  arteries). 

When  examined  in  the  early  stages  of  degeneration  the  muscula- 
ture of  these  peripheral  arteries  shows  a  fatty  change,  while  the 
intima  may  remain  quite  normal.  The  muscle  fibres  are  first  at- 
tacked and  later  the  elastic  fibres  are  also  involved,  until  eventually 
the  process  exhibits  a  fatty  degeneration  or  destruction  of  all  the 
elements  in  the  area  attacked.  Seldom  do  we  find  the  pure  fatty 
degeneration  proceed  to  this  stage  without  the  presence  of  asso- 
ciated calcium  salts  within  it,  and  at  the  same  time  fatty  acids,  both 
free  and  combined,  may  be  demonstrated. 

From  this  stage  on,  all  grades  of  calcification  of  the  arteries  are 
found.  The  simpler  cases  show  a  granular  deposi]:,  the  more 
severe  forms  show  the  calcareous  salts  welded  together  in  solid 
masses  completely  encircling  the  arteries.  There  is  in  this  process 
no  type  of  true  calcification  in  living  cells.  Where  calcification 
exists,  there  has  been  a  destruction  of  tissue  in  whose  place  have 
been  left  the  fatty  particles  of  the  degenerated  cells,  so  that  in  some 
stage  of  the  calcareous  degeneration  of  the  arteries,  a  fatty  process 
can  be  demonstrated,  and  that  in  the  progressive  process  of  calcifi- 
cation- only  small  quantities  of  fatty  acids  free  and  combined  are 
to  be  found.  It  is  not  fully  understood  whether  the  doubly  refrac- 
tile  particles  described  by  Adami  and  Aschoff,  have  anything  to  do 
with  the  liberation  of  free  fatty  acids  which  combine  with  the  cal- 
cium salts.  In  these  calcified  areas  the  calcium  phosphate  is  much 
in  excess  of  the  carbonate  (Wells),  which  allows  the  demonstration 
of  these  salts  by  von  Kossa's  method  with  silver  nitrate.  This 
method  is  still  the  best  to  demonstrate  the  presence  of  small  quanti- 
ties of  calcium  (phosphate)  in  the  arteries.  Larger  quantities  of 
fatty  substance  in  and  about  the  calcified  areas  than  are  exhibited 
by  the  direct  application  of  Sudan  III,  are  obtained  if  the  areas  are 
first  decalcified.  It  is  found  that  some  of  the  calcium  salts  are 
linked  to  the  fatty  substances  and  thus  prevent  the  fat  from  stain- 
ing with  Sudan  III.  This  has  been  best  shown  in  the  experimen- 
tally calcified  arteries  of  rabbits. 

It  is  not  infrequently  noted  that  the  vessels  of  the  muscular  type 


54  Arteriosclerosis.    Diseases  of  the  Media. 

may  be  so  completely  calcified  as  to  present  rigid  tubes,  which  can 
be  grasped  at  one  end  and  raised  without  kinking.  This  process, 
regardless  of  the  etiological  factor,  has  no  connection  with  the  in- 
timal  arteriosclerosis  in  other  parts  of  the  body,  though  neverthe- 
less the  two  may  and  do  occur  m  the  same  subject,  and  we  must 
agree  with  Moenckeberg  and  Marchand  that  the  presence  of  arter- 
iosclerotic changes  in  the  radial  and  other  peripheral  arteries  is  no 
proof  of  arterial  disease  in  the  aorta  or  other  internal  vessels. 

This  process  of  calcification  of  the  peripheral  arteries  bears  no 
relation  to  inflammatory  conditions  in  the  media,  and  is  always  a 
degenerative  process  from  the  beginning.  What  relationship  there 
may  be  to  alterations  in  the  vasa  vasorum  remains  undecided.  It 
may  be  that  the  isolated  and  patchy  way  in  which  the  degenerated 
areas  arise,  have  their  origin  in  endarteritis  or  thromboses  of  the 
vasa  vasorum  by  which  means  the  nutrition  of  the  media  is  severely 
interfered  with.  We  do  know,  however,  that  the  calcareous  de- 
generation of  the  peripheral  arteries  is  sometimes  the  result  of 
overwork  and  high  blood  pressure  within  them.  This  is  evident 
in  individuals  whose  continual  occupation  requires  excessive  use  of 
certain  limbs.  In  most  individuals  the  femoral  arteries  are  most 
frequently  affected,  while  in  the  upper  extremities  the  right  radial 
shows  a  greater  involvement  than  the  left  (in  right-handed  per- 
sons). AVe  have  repeatedly  demonstrated  the  extensive  sclerotic 
conditions  of  the  iliac  and  femoral  arteries  in  individuals  (as  police- 
men) who  are  much  on  their  feet.  In  females  over  forty  years 
the  uterine  arteries  commonly  show  calcification  of  the  media.  All 
these  vessels  are  such  as  from  time  to  time  are  taxed  by  repeated 
increase  of  blood  pressure,  which  necessarily  must  be  withstood 
by  the  media. 

In  studying  the  question  of  arteriosclerosis  (medial)  in  its  rela- 
tion to  occupation,  we  have  been  impressed  by  several  points.  It 
has  become  quite  evident  that  the  vessels  supplying  those  regions 
which  are  most  active  are  more  subject  to  degenerative  diseases 
than  the  corresponding  vessel  of  the  opposite  side.  This  is  like- 
wise true  of  the  vessels  of  the  internal  organs,  when  one  of  a  paired 
organ  (kidney)  is  functionating  more  actively  than  the  other.  In 
these  cases,  we  are  led  to  conclude  that  the  process  of  degeneration 


Diseases  Affecting  the  Media.  55 

follows  a  condition  o£  overstrain  which  has  been  long  continued. 
The  condition  of  overstrain  may  result  from  increased  blood  pres- 
sure brought  on  by  circulatory  disturbances  elsewhere  in  the  body, 
or  the  artery  itself  may  be  in  a  condition  of  "  hypertonus  "  (Rus- 
sel).  In  any  event,  a  continuation  of  either  condition  leads  to  a 
fatigue  of  the  arterial  wall  with  a  slow  process  of  degeneration 
beginning  in  the  vessel.  As  strain  acts  mainly  upon  the  media  of 
the  artery,  it  is  this  coat  which  suffers  when  fatigue  sets  in.  These 
processes  of  fatigue  indicate  nutritional  and  functional  alterations 
in  the  muscle  fibres,  which  are  best  demonstrated  by  the  fat  drop- 
lets aggregated  about  the  nucleus.  Still  more  severe  alterations  in 
the  muscle  fibres  lead  to  the  deposition  of  calcareous  salts  in  the 
debris  of  the  injured  cells. 

An  analogous  type  of  medial  calcification  also  occurs  in  the 
arteries  of  the  elastic  tissue  type.  Here,  where  the  muscular  bands 
of  the  media  are  separated  by  lamellae  of  elastic  fibres  such  a  firm 
calcification  of  the  muscle  tissue  cannot  take  place.  It  is  almost 
constantly  found,  as  I  have  described  elsewhere,  that  in  persons 
over  fifty  years  of  age — and  frequently  in  those  over  forty-five — 
the  media  of  the  aorta  shows  microscopically  calcareous  degenera- 
tion. In  such  aortas  I  have  frequently  noted  the  absence  of  any 
macroscopic  change  in  the  intima  or  the  media,  and  yet  have 
found  that  microscopically  there  was  an  extensive  loss  of  the  mus- 
cular elements,  their  place  being  taken  by  a  fine,  granular  deposit  of 
calcium  salts.  This  calcium  deposit  lies  between  the  elastic  lamellae, 
and  in  the  sites  where  the  muscle  elements  have  disappeared.  In 
these  cases  too  a  fatty  degeneration  can  be  demonstrated  in  the 
muscle  cells  which  are  undergoing  necrobiosis.  The  calcium  deposit 
is  readily  demonstrated  in  frozen  sections,  treated  with  a  five  per 
cent,  solution  of  silver  nitrate  and  counterstained  with  safranin,  or 
it  may  also  be  seen  in  well-stained  hsematoxylin  preparations.  The 
calcareous  degeneration  of  the  muscle  fibres  is  limited  more  or  less 
to  a  band  occupying  the  middle  zone  of  the  media.  That  portion 
of  the  media  lying  close  to  the  intima,  and  that  layer  bordering  the 
adventitia  are  free  from  degenerative  processes,  and  in  these  parts 
the  muscle  cells  are  well  preserved.  It  is  also  striking  that  the 
muscle  elements  about  the  vasa  vasorum,  no  matter  in  which  portion 


56  Arteriosclerosis.    Diseases  of  the  Media. 

of  the  media  they  are  found,  are  without  degenerative  changes. 
From  these  evidences  and  the  fact  that  the  degeneration  occurs  con- 
stantly in  old  age,  without  regard  to  any  particular  etiological 
factor,  I  was  led  to  conclude  it  to  be  a  true  senile  arteriosclerosis. 
There  is  no  arterial  disease  which  truly  deserves  the  name  of  "  Ab- 
nutzungs  Arteriosclerose  "  (Aschoff )  more  than  this.  This  senile 
arteriosclerosis  results  from  gradual  loss  of  nutrition  and  the  long 
period  of  work, — the  true  rust  of  life.  No  doubt,  in  the  autumn 
of  life,  the  cells  of  the  intima  and  the  elements  of  the  vasa  vasorum 
are  less  active  in  distributing  nourishment  to  the  vessel  wall.  Not 
uncommonly  the  vasa  vasorum  of  these  arteries  show  definite 
changes  and  thickening.  The  lymphatics  too  in  all  the  coats  of 
the  artery  become  clogged,  to  the  disadvantage  of  carrying  off  the 
effete  products.  Necessarily  then  that  part  of  the  arterial  wall 
farthest  away  from  the  supply  of  nourishment  will  suffer  the 
most, — and  this  is  the  middle  layer  of  the  media. 

This  calcareous  degeneration  of  the  media  is  distinguished  by 
being  uniformly  distributed  in  the  middle  zone  of  all  parts  of  the 
aorta,  and  in  being  deposited  in  fine  sand-like  granules  which  are 
evident  only  after  treatment  with  silver  nitrate,  and  by  the  micro- 
scope. 

True  atheroma  with  its  sequel,  calcification,  is  a  process  begin- 
ning and  usually  confined  to  the  intima.  Every  now  and  again, 
however,  we  meet  with  this  condition  in  the  aorta,  so  advanced  that 
the  vessel  in  general  appears  very  shaggy.  The  intimal  surface 
is  rough,  and  small  firm  sphnters  of  calcified  plaques  project  into 
the  lumen.  The  vessel  wall  is  commonly  very  brittle  and  its  tissues 
appear  dry,  so  that  different  layers  can  be  peeled  from  the  surface. 
If  we  examine  such  a  specimen,  we  find  that  in  many  places  the 
extensive  atheromatous  process  with  calcification  lies  not  only  in 
the  intima  but  also  in  the  upper  layers  of  the  media.  In  such  in- 
stances, this  degenerative  process  of  atheroma  has  advanced  to  the 
middle  coat  from  the  intima.  It  is  only  in  such  secondary  medial 
processes  that  atheroma  is  found  in  the  middle  coat.  True  athe- 
roma with  its  calcification  seldom  if  ever  arises  primarily  in  the 
media. 


Diseases  Affecting  the  Media.  57 

Bone  and  Cartilage  in  the  Media. — The  literature  contains  a 
considerable  number  of  reports  of  the  finding  of  bone  in  the  tissues 
of  the  arteries.  Very  little  reliance  can  be  placed  on  the  reports 
of  "  ossified  arteries  "  prior  to  Virchow's  discussion  in  1862,  in 
which  he  sets  forth  the  differentiation  of  "  calcification  "  and  "  ossi- 
fication." Many  of  the  older  writers  used  the  expression  "  ossi- 
fication "  very  loosely,  referring  to  both  the  process  of  bone  for- 
mation, and  of  calcium  deposit. 

At  first  sight  it  may  seem  out  of  place  to  discuss  the  subject  of 
bone  and  cartilage  formation  in  the  arteries,  under  the  "  degenera- 
tions." At  the  outset  we  must  admit  that  here  our  classification 
is  open  to  discussion,  but  after  considering  the  processes  involved 
in  these  lesions,  we  felt  justified  in  entering  the  discussion  imme- 
diately after  the  calcareous  degenerations  rather  than  with  the  pro- 
ductive processes. 

Rokitansky,  Andral  and  others  refer  to  the  occurrence  of  bone 
in  the  aorta  as  a  common  finding,  but  these  authors  did  not  make 
it  clear  that  they  were  not  dealing  with  calcareous  plaques.  In 
1862,  Virchow  not  only  pointed  out  the  difference  between  ossified 
and  calcified  tissue,  but  he  described  an  actual  case  of  bone  forma- 
tion in  the  arterial  wall.  As  the  instances  of  true  bone  were  un- 
usual, Virchow's  findings  were  for  a  time  denied  (Rindfleisch). 
Nevertheless  heteroplastic  bone  was  demonstrated  in  various  organs 
in  the  body  and  in  muscle  tissue,  and  soon  after  new  cases  of 
osseous  and  osteoid  tissue  in  the  arterial  walls  were  described  by 
different  authors  (Orth,  Ziegler,  Cohn,  Rhoemer  and  others). 

When  we  review  the  instances  of  bone  formation  in  the  arteries, 
we  find  that  the  majority  have  occurred  in  the  media,  while  the 
remainder  have  developed  in  the  intima.  In  all  instances  regard- 
less of  the  site,  this  new  bone  develops  in  the  region  of  previous 
disease,  and  usually  there  is  evidence  of  former  calcification. 
Moreover,  when  the  lesions  are  observed  during  their  progressive 
stage,  there  are  evidences  of  connective  tissue  and  vascular  prolifer- 
ation in  or  about  the  calcified  area. 

Cohn  observed  that  the  process  of  bone  formation  in  arteries 
developed  in  two  stages,  (a)  a  fracture  of  the  calcareous  ring  in 
the  media  with  a  secondary  granulation  tissue,  and  (&)  the  devel- 


58  Arteriosclerosis.    Diseases  of  the  Media. 

opment  of  osteoid  tissue  with  marrow  spaces.  The  osteoid  tissue 
he  beheved  resulted  from  a  metaplasia  of  the  connective  tissue. 
Bensen  describes  bone  formation  in  the  calcified  media  of  the  ves- 
sels of  the  leg  in  a  case  of  diabetes,  and  other  instances  in  the 
same  vessels  are  given  by  Rhoemer,  and  by  Buerger  and  Oppen- 
heimer. 

Moenckeberg  systematically  examined  a  hundred  cases  of  ad- 
vanced arteriosclerosis  and  found  bone  present  in  ten  per  cent,  of 
the  vessels.  Similar  observations  were  made  by  Howse,  O'Brien, 
Marchand  and  others. 

In  a  few  instances  the  areas  containing  the  bone  deposits  were 
found  to  be   surrounded  by   cartilage    (Rosenstein,    Marburg). 

As  an  accidental  finding,  and  in  no  way  suggesting  the  incidence 
of  the  process,  I  have  observed  bone  formation  in  the  media  in 
two  cases,  and  once  in  the  intima.  In  the  latter  instance  an  old 
thrombus  occluded  the  vessel,  while  in  the  former  cases  the  arteries 
showed  a  very  marked  Moenckeberg  arteriosclerosis. 

It  is  extremely  interesting  that  these  lesions  have  been  repro- 
duced in  animals  by  a  few  investigators.  Sacerdotti  and  Frattin 
were  able  to  demonstrate  bone  in  the  renal  arteries  three  months 
after  these  vessels  had  been  ligated.  Harvey  obtained  the  same 
results  by  painting  a  solution  of  copper  sulphate  or  silver  nitrate  on 
the  outside  of  the  aorta  of  rabbits.  Harvey  reports  that  bone  with 
Haversian  canals  developed  in  the  tunica  media  in  areas  which  had 
previously  been  extensively  calcified  and  that  a  tissue  not  unlike 
cartilage  was  also  formed. 

All  authors  are  not  agreed  upon  the  mode  in  which  the  bony 
tissue  is  developed.  But  the  observations  are  fairly  constant  in- 
dicating that  a  process  of  extensive  calcification  precedes  the 
osseous  deposit.  Some  believe  that  the  mere  presence  of  the  cal- 
careous nodule  attracts  the  vascular  structures  to  it  (Rhoemer), 
others  consider  that  fractures  in  the  calcified  masses  offer  the 
stimuli  for  the  development  of  a  callous-like  development,  which 
carries  with  it  blood  vessels  and  connective  tissue  (Cohn,  Paul 
and  Bunting). 

Opinion  is  also  divided  as  to  where  the  bone  cells  arise  which 
surround  the  area  of  initial  calcification.      Some  argue  that  the 


Diseases  Affecting  the  Media.  59 

bone  cells  can  arise  only  from  cartilaginous  or  osteogenic  tissues, 
and  that  those  in  the  arteries  must  arise  from  the  usual  foci  of  bone 
cells  (Ribbert,  Busch  and  Hansemann).  On  the  other  hand  the 
majority  of  investigators  are  convinced  that  bone  cells  may  be 
derived  in  a  process  of  metaplasia  from  connective  tissue.  In  the 
case  of  the  bone  formation  in  the  arteries  it  is  evident  that  the 
young  granulation  tissue  which  advances  to  and  surrounds  the 
primary  calcification  plays  a  very  important  function  in  the  future 
development  of  bone.  During  the  process,  the  connective  tissue 
cells  become  closely  opposed  to  the  calcareous  masses,  and  transi- 
tions can  be  observed  between  the  adult  fibrous  tissue  cells  and 
the  small  bone  corpuscles.  Giant-cells,  osteoclasts,  osteoblasts  and 
bone  cells  are  all  to  be  observed.  At  times  the  new  structure  con- 
tains no  lime  salts  (osteoid),  though  the  cellular  arraiigement  is 
that  of  bone. 

There  seems  little  doubt  that  connective  tissue  may  become  en- 
dowed, if  the  proper  stimuli  are  present,  with  the  properties  of  bone 
cells.  From  the  observations  made  on  bone  in  arteries,  the  stimu- 
lus lies  in  the  presence  of  calcareous  masses  surrounded  by  granu- 
lation tissue.  At  the  points  of  contact,  the  connective  tissue  cells 
lying  against  the  lime  deposit  take  on  the  characters  of  bone  cor- 
puscles. . 

Hyaline  and  Amyloid  Degeneration  of  the  Media. — Two  other 
types  of  medial  degeneration  of  arteries  are  very  interesting,  but,  as 
we  have  stated  above,  hardly  come  under  the  term  arteriosclerosis, 
unless  the  word  is  used  in  the  broadest  sense.  These  are  the  hyaline 
and  the  amyloid  degenerations. 

Although  these  two  types  of  degeneration  occur  under  widely 
different  conditions,  yet  they  have  some  features  in  common.  Both 
occur  in  the  arteries  of  the  muscular  type,  and  seldom,  if  ever, 
develop  in  the  aorta  or  its  main  branches.  Both  occur  in  the  deep 
portion  of  the  intima,  or  associated  with  destruction  of  the  muscle 
cells  of  the  media. 

Little  is  known  as  yet  concerning  the  nature  and  origin  of  these 
substances,  and  still  less  is  known'  of  the  manner  in  which  they  are 
deposited.  It  may  be  that  there  is  some  chemical  relationship  be- 
tween the  hyaline  and  amyloid  deposits. 


60  Arteriosclerosis.    Diseases  of  ilie  Media. 

Some  confusion  has  developed  in  the  use  of  the  term  hyaHne,  so 
that  we  find  in  histological  descriptions  of  tissues,  a  considerable 
variation  in  the  meaning  inferred.  The  word  h^-aline  has  come  to 
be  used  to  express  any  bland  or  homogeneous  appearance,  without 
reference  to  the  nature  of  the  substance  under  discussion.  Though 
the  chemistry  of  hyaline  bodies  is  not  determined,  they  probably 
belong  to  the  phosphorus-free  glycoproteids,  and  result  from  the 
breaking  down  of  cell  protoplasms. 

The  hyaline  deposits  found  in  the  media  of  arteries  bear  no  rela- 
tion to  the  homogeneous  looking  connective  tissue  so  often  seen  in 
the  pearly  plaques  of  endarteritis  deformans. 

Hyaline  degeneration  of  the  media  is  most  commonly  met  with 
in  the  arteries  of  the  ovaries  and  uterus,  and  less  frequently  in  the 
arteries  of  the  thyroid,  spleen  and  adrenal. 

Clark,  in  1900,  studied  the  arteries  of  the  ovary,  and  found  that 
during  the  development  of  the  corpus  luteum,  new  arteries  advanced 
to  this  body.  These  vessels  remained  active  during  the  progressive 
changes  in  the  corpus.  As  soon,  however,  as  the  corpus  luteum 
showed  degenerative  changes,  the  arteries  passing  to  it  showed  hya- 
line changes  in  their  walls.  This  hyaline  change  began  in  the  adven- 
titia  and  advanced  into  the  media.  The  muscle  fibres  of  the  media 
apparently  break  down  and  the  detritus  of  the  different  cells  fuses 
into  one  homogeneous  mass.  Before  the  mass  is  properly  fused, 
the  degenerated  material  is  quite  granular,  and  contains  considerable 
quantities  of  fat.  A\^oltke  described  similar  changes  in  the  ovarian 
arteries,  which  were  not  associated  with  degenerating  corpora  lutea. 

Boeshagen  found  that  the  hyaline  degenerative  process  was  at 
times  so  extensive  that  the  media  and  adventitia  were  completely 
replaced  by  a  hyaline  substance,  and  that  the  endothelium  alone 
clothed  the  lumen  of  the  vessel.  In  some  instances  he  found  a  newly 
developed  layer  of  muscle  fibres  inside  of  the  hyaline  substance,  so 
that  it  appeared  to  him  that  a  new  vessel  had  formed  inside  of  the 
old  one. 

In  studying  the  vessels  of  the  uterus,  Szasz-Schwartz  observed 
that  the  musculature  of  the  arteries  was  at  times  replaced  by  a  sub- 
stance having  some  of  the  qualities  of  elastin.  These  degenerations 
are   shown  to   occur  most   commonly   after   repeated  pregnancies 


Diseases  Ajfectmg  the  Media.  61 

(Pankow).  This  author  has  also  shown  that  prohferative  changes 
similar  to  those  in  the  ovarian  arteries  develop  a  new  layer  of 
muscle  fibres  beneath  the  endothelial  layer,  and  diminish  the  size  of 
the  lumen. 

Similar  reports  of  the  hyaline  degeneration  of  the  media  of  the 
arteries  of  the  ovaries  and  uterus  have  been  made  by  Sohma  and 
Goodall  respectively.  Goodall  however  believes  that  the  degenera- 
tive changes  are  closely  associated  with  alterations  in  the  internal 
elastic  lamina. 

Mention  must  also  be  made  of  the  peculiar  hyaline  deposit  which 
takes  place  particularly  about  the  vessels  in  some  tumors.  In  cer- 
tain peritheliomata  there  is  found  a  narrow  layer  of  hyaline  material 
immediately  outside  the  endothelial  cells  of  both  the  capillaries  and 
the  smaller  arteries.  In  the  latter  vessels  the  hyaline  substance  may 
invade  and  replace  the  muscular  tissue  entirely. 

Although  amyloid  degeneration  of  the  arteries  bears  some  rela- 
tion to  the  hyaline  degenerations,  it  has  some  characteristic  features 
which  differentiate  it.  It  consists  in  the  deposit  of  a  homogeneous 
firm  substance  which,  when  present  in  large  quantities,  can  be 
recognized  by  the  naked  eye.  When  smaller  quantities  are  present, 
their  appearance  can  be  intensified  by  certain  reagents  (iodine,  or 
aniline  dyes).  It  is  found  however,  that  the  amyloid  deposits 
which  do  not  give  constant  microchemical  color  reactions,  differ  in 
their  composition. 

Amyloid  deposits  are  more  commonly  found  in  association  with 
chronic  suppurative  conditions  or  progressive  chronic  infections. 
In  these  instances  the  amyloid  degeneration  does  not  occur  about  the 
suppurative  process,  but  in  organs  and  tissues  in  remote  parts  of  the 
body.  The  kidney,  spleen  and  liver  are  especially  prone  to  be 
affected,  while  less  commonly  is  the  mucosa  of  the  stomach,  intes- 
tine, oesophagus,  trachea  and  bladder  involved. 

In  the  former  instances,  the  deposit  takes  place  in  and  about  the 
vascular  channels,  while  in  the  latter,  it  bears  some  relation  to  the 
epithelial  structures.  In  the  kidney,  spleen  and  liver  the  early  amy- 
loid deposits  occur  about  the  walls  of  the  capillaries,  immediately 
outside  of  the  endothelial  tube.  With  more  extensive  deposits,  the 
amyloid  substance  is  also  found  in  the  chinks  between  the  connective 


62  Arteriosclerosis.    Diseases  of  the  Media. 

tissue  cells.  The  arterioles  also  become  involved,  and  an  amyloid 
deposit  results  in  the  media.  Here  it  is  found  that  the  homogeneous 
substance  infiltrates  the  middle  coat  and  lies  between  the  muscle 
fibres,  but  not  actually  invading  the  cells.  Gradually  as  the  accumu- 
lation becomes  very  extensive,  the  muscle  fibres  are  compressed  and 
have  their  nutrition  interfered  with.  A  secondary  atrophy  and  de- 
generation thus  takes  place  in  these  cells. 

When  the  degenerative  process  is  advanced,  the  entire  media  may 
become  replaced  by  amyloid  substance,  so  that  a  thick  band  encircles 
the  vessel.  The  intima  frequently  becomes  thickened  by  a  con- 
nective tissue  hyperplasia,  and  the  lumen  of  the  vessel  is  narrowed. 

Little  information  is  at  hand  concerning  the  process  of  amyloid 
deposit,  nor  is  its  chemical  nature  at  all  clear. 


EXPERIMENTAL  MEDIAL  DISEASES  OF  ARTERIES. 

Our  knowledge  concerning  the  process  and  progress  of  medial  dis- 
ease of  arteries  has  been  much  enhanced  by  the  studies  on  experi- 
mental arteriosclerosis.  By  this  means  known  agents  were  admin- 
istered to  different  animals  over  definite  periods  of  time  and  the 
effects  of  these  agents  on  the  circulatory  system  was  observed.  To 
prove  of  value,  all  such  experiments  had  to  be  controlled  by  un- 
treated animals  living  under  the  same  conditions.  In  our  own  ex- 
periments, only  animals  bred  from  our  own  stock  were  used.  More- 
over, the  control  animals  were  "brothers"  from  the  same  litter,  so 
that  the  ages  of  the  animals  were  equal.  As  nearly  as  possible 
animals  of  equal  weight  and  rabbits  from  seven  to  eight  months  old 
were  selected.  At  the  conclusion  of  each  experiment,  due  care  must 
be  taken  to  examine  at  autopsy  for  any  intercurrent  disease. 

In  our  healthy  stock  of  animals,  where  no  aged  or  preA'iously  ex- 
perimented animals  are  used,  we  have  not  met  with  spontaneous 
arterial  disease  in  young  rabbits.  Like  others  we  haA'e  noted  the 
presence  of  isolated  medial  plaques  in  old  animals. 

We  agree  with  many  that  great  care  must  be  taken  in  comparing 
the  results  of  experimental  arterial  disease,  with  arteriosclerosis  of 
man.  This  statement  likewise  holds  for  all  experimental  work  on 
animals,  but,  nevertheless,  when  the  facts  of  the  experiments  are 
properly  arranged,  and  when  the  various  observations  have  been 
duly  weighed,  we  are  able  to  arrive  at  some  conclusion  respecting 
the  process  or  processes  at  work  in  the  given  experiment.  If  any 
of  the  truths  obtained  in  the  experiment  have  a  broad  significance, 
it  may  be  that  we  may  then  apply  them  to  similar  processes  in  man. 

We  can  by  no  means  agree  with  the  pessimist  and  the  destructive 
critic  that  experimental  arteriosclerosis  and  the  study  of  arterial  dis- 
eases in  animals  throws  no  new  light  upon  arterial  diseases  in  the 
human  subject. 

By  experimental  means  there  have  been  reproduced  types  of 
arterial  disease,  analogous  to  almost  every  type  of  arteriosclerosis 

63 


64  Arteriosclerosis.    Diseases  of  the  Media. 

in  man.  An  excellent  review  of  this  work  is  obtained  in  Saltykow's 
comprehensive  article. 

In  much  the  greater  number  of  experiments  rabbits  have  been 
used.  This  for  two  reasons — on  account  of  the  ease  with  which 
these  animals  are  handled  and  controlled,  and  because,  for  reasons 
yet  unexplained,  arterial  lesions  are  very  readily  produced.  Dogs 
and  cats  have  been  tried  with  only  partial  success.  These  animals 
respond  to  weaker  stimuli  by  hypertrophy  of  the  tissues  of  the 
various  coats,  but  degenerative  changes  are  not  so  readily  produced, 
save  when  coupled  with  a  general  derangement  of  metabolic  proc- 
esses, and  more  particularly  kidney  lesions. 

Experimental  Productive  Lesions  of  the  Media. — Fischer  and  v. 
Schmieden  have  shown  that  an  hypertrophy  of  the  media  develops 
when  the  internal  pressure  of  a  vessel  is  increased.  It  was  noted 
that  when  the  distal  end  of  the  severed  jugular  vein  was  united  to 
the  proximal  end  of  the  artery,  there  developed  not  a  functional 
hyperplasia  of  the  intima,  but  an  hypertrophy  of  the  media.  In  the 
main  the  muscular  fibres  of  the  vein  reacted  to  this  extra  strain  of 
arterial  blood  pressure,  while  only  occasional  intimal  thickenings  of 
an  inflammatory  nature  were  observed.  This  is  quite  similar  to  the 
process  which  we  have  described  above  as  occurring  in  man,  save 
that  in  the  larger  arteries  the  musculo-elastic  layer  of  the  intima 
may  also  partake  in  the  hypertrophy. 

Other  productive  lesions  of  the  media,  of  an  inflammatory 
nature,  have  been  produced  by  different  means.  Saltykow,  by  the 
injection  of  staphylococci,  besides  obtaining  arteriosclerosis  with 
atheroma  in  the  intima,  found  various  grades  of  fibrosis  in  the 
media.  In  some  instances  small  collections  of  leucocytes  were 
observed,  in  others  the  tissue  changes  were  more  advanced  with 
connective  tissue  infiltration. 

Similar  productive  lesions  result  from  mechanical  injury  to  the 
vessel  wall,  while  the  direct  application  of  various  drugs  to  the 
artery  has  been  shown  to  lead  to  a  localized  inflammation  which 
involves  the  adventitia  and  media.  The  simplest  mechanical  dam- 
age is  made  by  crushing  the  artery  with  haemostatic  forceps  (D'Anna 
and  Malkoff).    A  true  mesarteritis  and  periarteritis  is  obtained. 

The  production  of  a  septic  process  close  to  an  artery  also  leads 


Experimental  Medial  Diseases  of  Arteries.  65 

to  an  inflammatory  reaction  in  the  arterial  tissues.  These  condi- 
tions of  acute  periarteritis  have  been  the  common  result  in  trans- 
planted vessel  segments.  Should  the  vascular  tissues  be  severely 
involved  with  greater  or  less  septic  destruction  of  the  adventitia  and 
media,  a  localized  aneurysm  may  follow. 

The  nature  of  the  reaction  in  the  media  following  the  inoculation 
of  bacteria  is  dependent  upon  the  nature  of  the  organism,  the  num- 
bers of  the  organism  and  the  resistance  of  the  tissues.  By  these 
bacterial  inoculations  we  have  learned  that  different  bacteria  have  a 
varying  selective  action  on  the  tissue  cells.  Streptococcus  infection 
affects  mainly  the  intima  in  proliferation  (Sumikawa  and  Klotz)  ; 
diphtheria  (toxins)  act  destructively  upon  the  media  (Klotz)  ;  while 
staphylococci  produce  both  proliferative  and  degenerative  lesions  in 
the  intima  and  media  of  the  arteries  (Sumikawa  and  Saltykow). 

It  is  unnecessary  to  describe  in  detail  the  histological  changes 
developing  in  the  different  lesions,  suffice  it  to  say  that  they  bear 
a  close  resemblance  to  the  changes  found  in  man. 

Chronic  productive  mesarteritis  has  also  been  produced  in  animals 
through  the  agency  of  tuberculosis  and  glanders  (Duval).  With 
the  arterial  changes  in  experimental  syphilis  we  are  not  familiar. 

Experimental  Degenerative  Medial  Disease. — By  far  the  greater 
number  of  experiments  aiming  at  the  production  of  arteriosclerosis 
in  animals  have  led  to  this  result.  The  earlier  experiments  on  ani- 
mals were  carried  on  by  using  mechanical  procedures,  and  as  we 
have  observed  above,  various  grades  of  inflammation  were  produced 
in  one  or  more  coats.  These  experiments  only  indicated  that  the 
arterial  wall  was  subject  to  inflammation  and  that  the  inflammatory 
reaction  of  the  intima  differed  from  that  found  in  the  media  or 
adventitia.  The  so-called  nervous  scleroses  of  experimental  animals 
were  found  to  be  nothing  else  than  secondary  inflammatory 
reactions. 

It  was  not  until  Josue,  in  1904,  observed  that  the  repeated  admin- 
istration of  adrenalin  over  some  weeks,  produced  in  rabbits  definite 
arterial  lesions  of  a  degenerative  character,  that  the  experimental 
work  in  arteriosclerosis  received  a  new  impetus.  Laboratories  had 
been  looking  for  such  a  substance,  and  with  the  suggestion  that  the 
active  factor  in  adrenalin  was  in  its  blood-pressure  raising  action,  a 


66  Arteriosclerosis.    Diseases  of  the  Media. 

great  many  other  drugs  of  similar  qualities  were  tried.  Such  other 
drugs  produced  lesions  quite  similar  to  adrenalin  (nicotin,  digitalin, 
hydrastin  and  barium  chloride). 

By  the  use  of  these  substances,  we  have  been  able  to  follow  the 
process  of  degeneration  of  the  media  from  its  earliest  stage.  In 
these  experiments,  rabbits,  too,  have  served  the  greatest  usefulness, 
and  in  these  animals  the  aorta  has,  on  account  of  the  frequency  of 
the  lesions,  been  most  thoroughly  examined.  It  has  been  shown 
that  those  drugs,  exhibiting  an  increase  in  the  blood  pressure,  are 
particularly  prone  to  attack  the  media,  and  to  produce  in  it  lesions 
quite  comparable  with  the  medial  calcification  of  the  peripheral 
vessels  in  man.  Although  the  structure  of  the  rabbit's  aorta  is 
similar  to  that  of  the  arteries  of  the  elastic  tissue  type  in  man,  and 
thus  is  different  from  the  muscular  vessels  of  the  extremities,  never- 
theless, the  lesions  called  forth  in  these  two  types  of  artery  are  com- 
parable. As  I  have  shown  above,  there  is  a  medial  disease  of  the 
aorta  in  man,  which  although  milder  in  grade,  is  of  the  same  nature 
as  the  process  of  calcification  in  the  vessels  of  the  extremities.  So 
here  also  in  the  rabbit's  aorta,  the  process  simulates  that  in  the 
media  of  the  human  aorta,  but  is  much  more  severe  in  type.  In  the 
rabbit,  not  alone  do  the  muscle  fibres  undergo  degeneration  and 
destruction  but  also  the  elastic  fibres  which  lie  between  the  muscle 
bands.  In  the  muscle  fibres,  the  fine  granular  fatty  degeneration  at 
length  gives  way  to  a  coarsely  granular  one,  until  the  muscle  cell 
dies  and  leaves  the  fat  droplets  in  situ.  I  must  emphasize  that  these 
free  fat  granules  have  come  from  broken  down  muscle  fibres,  and 
are  not  developed  by  a  pressing  out  of  the  fat  from  the  serous  fluids, 
as  Ribbert  would  have  it  in  the  intima.  To  be  emphasized  too,  is 
that  these  patches  of  fatty  degeneration  develop  away  from  the 
vasa,  as  is  also  the  case  with  the  areas  of  fatty  degeneration  of  the 
heart.  Following  this  the  involved  area  becomes  calcified,  so  that 
not  infrequently  the  entire  aortic  tube  from  the  arch  to  the  renal 
presents  an  egg-shell  like  structure.  Microscopically,  it  is  seen  that 
the  process  is  localized  to  the  media,  while  in  most  cases  the  intima 
remains  intact.  The  earlier  stages  of  the  process  show  the  calcify- 
ing areas  to  be  distributed  irregularly  in  the  vessel  wall,  usually  in 
the  descending  thoracic,  and  as  the  disease  proceeds,  the  neighboring 


Experimental  Medial  Diseases  of  Arteries.  67 

plaques  fuse  to  form  larger  ones.  Like  both  the  aortic  and  the 
peripheral  arterial  (medial)  disease  in  man,  the  experimental  lesions 
occupy  the  middle  zone  of  the  media.  The  exact  action  of  these 
drugs  on  the  blood  vessels  is  still  a  matter  in  dispute,  some  main- 
taining that  the  increased  pressure  which  is  produced  in  the  arteries 
is  the  cause,  others  that  the  toxic  nature  of  the  substances  causes  a 
necrosis  of  the  muscle  fibres,  and  still  others  that  contraction  or 
thrombosis  of  the  vasa  vasorum  leads  to  a  mal-nutrition  of  the 
musculature.  In  my  recent  experiments  I  have  shown  that  an 
increased  pressure  in  the  arteries  can  in  itself  produce  this  medial 
calcification,  besides  producing  in  other  vessels  (carotid),  a  true 
intimal  arteriosclerosis,  with  splitting  of  the  elastic  fibres  and 
atheroma. 

I  have  found  that  when  a  rabbit  is  suspended  by  the  hind  legs  for 
three  minutes  every  day  over  a  period  of  one  hundred  and  thirty 
days,  that  the  media  of  the  aorta  shows  the  same  egg-shell  like 
calcification  as  had  been  produced  in  other  animals  by  the  inocula- 
tion of  adrenalin.  I  found  that  the  blood  pressure  in  the  carotids 
and  the  arch  of  the  aorta  is  increased,  and  that  the  lesions  in  the 
aorta  were  limited  to  the  parts  above  the  renal  arteries  and  more 
particularly  above  the  diaphragm.  The  vessels  of  the  lower  abdo- 
men and  the  lower  extremities  were  entirely  free  from  disease.  In 
short,  those  vessels  which  had  to  accommodate  themselves  to  a  high 
and  varying  blood  pressure  showed  medial  calcification. 

One  of  the  characteristics  of  experimental  medial  calcification  is 
that  the  vessel  wall  as  a  whole  is  thinned.  This  is  due  to  an  actual 
thinning  taking  place  in  the  media,  as  a  result  of  the  muscle  cells 
becoming  degenerated  and  the  elastic  lamellae  packed  closer 
together. 

To  obtain  a  proper  conception  of  the  fatty  degeneration  which 
bears  a  relationship  to  the  calcification  of  experimental  medial  dis- 
ease, one  must  not  only  stain  the  frozen  sections  directly  with  Sudan 
III,  but  some  sections  should  also  be  decalcified  before  the  stain  is 
applied.  Here  it  will  be  found  that  in  those  areas  in  which  the 
calcifying  process  is  not  complete,  there  are  abundant  fats  and  fatty 
acids. 

From  these  experimental  lesions  one  readily  sees  the  lack  of  inter- 


68  Arteriosclerosis.    Diseases  of  the  Media. 

dependency  between  the  lesions  of  the  media  and  those  of  the  intima. 
It  is  true  enough  that  under  certain  conditions  the  intimal  lesions 
will  lead  to  medial  alterations  and  vice  versa,  but  it  cannot  be  afore- 
said that  because  a  certain  agent  produced  a  degeneration  in  the 
media  that  a  definite  other  change  must  occur  in  the  intima. 

The  work  of  Josue  has  marked  a  new  era  in  the  study  of  arterial 
diseases.  His  successful  experiments  with  adrenalin  have  stimu- 
lated much  study  and  have  directed  our  attention  along  a  new  path  of 
thought.  Since  his  original  work  in  1903,  many  have  verified  his 
results,  and  others  have  shown  that  substances  having  somewhat 
similar  physiological  ef¥ects  as  adrenalin  will  also  bring  about 
medial  lesions. 

One  cannot  be  but  struck  by  the  fact  that  these  substances  (adre- 
nalin, nicotin,  hydrastin,  barium  chloride,  digitalin),  although 
differing  widely  in  their  chemical  composition,  have  a  common 
action,  the  temporary  raising  of  blood  pressure.  From  a  patho- 
logical standpoint,  they  also  have  a  common  result,  the  degeneration 
of  the  medial  tissues  of  the  arteries,  particularly  the  aorta.  It  has 
been  a  common  comment  that  the  arterial  lesions  produced  by  these 
various  high  blood-pressure  drugs  are  similar. 

In  the  interesting  work  of  transplanting  segments  of  vessels 
between  the  cut  ends  of  an  artery  some  important  observations  have 
been  made.  Guthrie  has  found  that  when  homoplastic  vessel  seg- 
ments are  rapidly  transferred  from  the  donee  to  the  host,  very  little 
change  may  occur  in  the  successful  graft.  The  major  part  of  the 
tissues  of  the  graft  persists  and  continues  to  live  in  the  new  host. 
Guthrie  finds,  however,  that  transplanted  segments  which  have  been 
in  formalin,  may  functionate  as  blood  channels,  but  only  as  passive 
agents.  These  formalined  specimens  act  as  a  temporary  framework 
upon  which  is  built  a  fibrous  tissue  coat,  while  the  lumen  may  be 
clothed  by  a  new  endothelial  lining.  He  has  obtained  similar 
results  with  heteroplastic  transplantations  of  arterial  segments.  In 
these  instances  the  muscle  fibres  of  the  media  are  observed  to  dis- 
appear first,  while  the  elastic  fibres  and  connective  tissue  may 
remain.  None  of  the  changes  which  have  been  observed  to  develop 
in  the  transplanted  segments  show  any  similarity  to  an  arterio- 
sclerotic process. 


Experimental  Medial  Diseases  of  Arteries.  69 

Carrel  claims  to  have  preserved  arterial  segments  in  a  condition 
of  latent-life  over  periods  of  many  days.  Such  segments  preserved 
in  the  cold  can,  he  says,  again  be  restored  to  active  life  by  trans- 
plantation into  an  active  circulation.  When,  however,  the  arterial 
segments  have  in  any  way  been  damaged  the  muscle  cells  are  among 
the  first  to  show  degenerative  changes. 


ETIOLOGICAL     FACTORS     CONCERNED     IN     MEDIAL 
DISEASE    OF    ARTERIES. 

As  may  be  gathered  from  what  has  previously  been  said,  there 
are  a  variety  of  factors  which  play  a  part  in  the  production  of  the 
medial  arteriosclerosis.  It  had  been  the  hope  of  many  investigators 
that  modern  pathological  technique  and  minute  studies  of  arterial 
disease  would  find  a  way  of  distinguishing  the  lesions  produced  by  a 
certain  agent  from  all  others.  AVe  are  familiar  to-day  that  such 
has  not  been  possible,  but  on  the  contrary  do  we  find  that  many 
and  widely  diverse  factors  produce  similar  arterial  disease.  More- 
over, it  is  found  that  a  given  agent  under  different  conditions  or  in 
different  amounts,  may  produce  many  types  of  lesions  in  the 
arteries.  So  we  come  to  recognize  that  it  is  quite  impossible  to 
indicate  from  the  t3'pe  of  lesion  present,  the  agent  which  had 
brought  about  the  result.  To  this  general  statement  we  must  admit 
of  at  least  one  exception.  Syphilis  of  the  aorta  can  usually  be 
recognized  by  the  naked  eye,  and  the  diagnosis  can  be  further  sub- 
stantiated by  the  histological  findings.  Occasionally  too,  in  tuber- 
culosis, tubercles  are  recognized  in  the  walls  of  the  arterioles,  par- 
ticularly of  the  brain. 

Hence,  much  as  we  should  like  to  speak  of  an  alcoholic  arterio- 
sclerosis, a  typhoid  arteriosclerosis,  a  lead  arteriosclerosis,  as  we  do 
of  a  syphilitic  arteriosclerosis,  it  is  impossible  to  do  so.  Neverthe- 
less, we  are  familiar  with  a  variety  of  agents  which  act  in  a  dele- 
terious manner  upon  the  middle  coat  of  the  walls  of  the  arteries 
which  may  be  classified  into  four  groups,  (i)  infections,  (2) 
poisons  and  toxins,  (3)  work,  and  (4)  old  age.  Besides  attri- 
buting medial  diseases  to  one  or  other  of  these  definite  agents,  there 
are  a  certain  few  pathological  conditions,  which  are  not  primary  in 
the  media  but  which  advance  from  the  intima  or  adventitia  into  the 
media.  It  is  quite  obvious  that  disease  processes  lying  deep  in  the 
intima,  may  overstep  the  imperfect  boundaries  between  the  con- 
tinguous  layers  and  advance  into  media.  Particularly  is  this  true 
of  infective  conditions  and  fatty  degenerations  of  intima.     These 

70 


Etiological  Factors.  71 

latter  conditions  probably  result  from  a  blockage  of  the  lymph 
channels  passing  from  the  intima  into  the  upper  layer  of  the  media, 
and  by  cutting  off  the  nutrition  from  the  vessel  lumen,  bring  on  slow 
degenerative  changes  in  the  muscle  cells  of  the  media. 

I.  Infection. — The  infections  are  probably  the  most  important 
agents  which  bring  about  productive  lesions  in  the  media.  Both 
with  them  as  with  all  other  influences,  the  important  point  rests  in 
the  amount  and  strength  of  the  dose  present.  AA'hen  at  times,  the 
infective  process  is  so  severe  that  the  tissue  elements  are  unable  to 
react,  the  lesion  has  the  characters  of  a  purely  degenerative  one, 
even  necrosis.  This  is,  however,  quite  infrequent,  and  is  met  with 
only  in  extensive  pygemic  conditions.  These  suppuratii'e  foci  in  the 
arteries  must  be  occasionally  distinguished  from  the  degenerative 
lesions  produced  by  the  toxins  of  the  bacteria.  Whereas,  the  pyo- 
genic bacteria  stimulate  inflammatory  processes  of  different  grades, 
the  bacterial  toxins  usually  act  on  the  tissues  in  a  destructive  manner 
without  stimulating  an  inflammatory  reaction.  The  toxins  of  the 
bacterial  organisms  act  directly  upon  the  tissues  of  the  media,  bring- 
ing about  fatty  changes  and  eventually  destruction  to  the  cells.  It 
has  been  found  experimentally  that  the  introduction  or  the  inocula- 
tion of  the  living  organisms  into  the  body  will  at  times  bring  about 
similar  degenerative  lesions  in  the  media. 

With  typhoid  fever,  the  results  are,  somewhat  different.  Here 
we  cannot  definitely  dissociate  the  effect  of  the  toxin,  and  the  result 
of  the  bacterial  invasion  itself.  In  the  human  subject,  the  common- 
est lesions  resulting  from  typhoid  fever  are  noted  in  the  intima  of 
the  aorta,  where  small  fatty  streaks  develop  in  the  deep  layers. 
These  fatty  areas  probably  result  from  the  degeneration  of  the 
longitudinal  muscle  fibres,  while  at  other  times  a  more  superficial 
fatty  deposit  is  found  in  the  subendothelial  connective  tissue.  Over 
some  of  these  areas  there  not  infrequently  develops  a  slight  endothe- 
lial thickening.  These  superficial  degenerative  processes  in  the 
intima  are,  I  believe,  the  effect  of  the  free  poison  or  endotoxin  cir- 
culating in  the  blood.  On  the  other  hand  the  septicsemic  typhoid 
infection  is  also  frequently  noted  by  the  presence  of  inflammatory 
infiltrations  along  the  vasa  vasorum  of  the  adventitia  and  media. 
These  cellular  infiltrations  I  have  not  obtained  in  animals  when  dead 


72  Arteriosclerosis.    Diseases  of  the  Media. 

cultures  were  inoculated  and  I  believe  we  are  right  in  concluding 
that  the  medial  inflammatory  infiltrations  are  the  result  of  the  inva- 
sion of  living  bacteria.  In  other  words,  when  the  infective  agent 
itself  circulates  in  the  blood  and  this  is  true  of  typhoid,  para-typhoid, 
B.  coli,  Streptococcus  and  Staphylococcus  infections,  and  the  micro- 
organisms become  localized  at  various  points  in  the  body,  the  tissues 
of  the  part  react  to  the  bacterial  irritation  by  inflammation.  Micro- 
scopically these  reactions  are  evident  in  the  accumulation  of  leuco- 
cytes or  if  the  process  is  healing  or  healed,  the  presence  of  excess 
fibrous  tissue  is  observed.  In  the  arteries,  these  accumulations  of 
inflammatory  exudates  are  found  about  the  vasa  vasorum  of  the 
larger  vessels  and  are  met  with  in  the  infections  above  mentioned. 
The  result  of  these  infections  of  the  vascular  tissues  is  the  develop- 
ment of  sporadic  medial  disease  of  the  productive  type. 

There  are  some  instances,  however,  in  which  localized  infection 
leads  to  abscess  formation  in  the  media.  The  fixed  tissues  of  the 
part  undergo  necrosis  and  leave  a  much  weakened  vessel  wall. 
Extensive  tissue  destruction  may  lead  to  aneurysm  or  even  rupture 
of  the  infected  arteries,  or  in  other  instances  when  healing  has 
taken  place,  the  lesion  is  replaced  by  considerable  scar  tissue  pro- 
ducing a  hardening  and  sclerosed  area  at  this  point. 

Occasionally  the  infective  agent  reaches  the  vessel  wall,  not  by  a 
septicaemic  process,  but  by  direct  continuity  through  the  lymphatics 
from  a  nearby  septic  focus.  This  type  is  most  often  met  with  in 
the  vessels  lying  in  or  about  infected  cavities  (tuberculosis)  in  the 
lungs.  The  process  is  of  importance,  as  it  is  one  of  the  frequent 
causes  of  rupture  of  these  arteries  with  fatal  haemorrhage.  Those 
vessels  which  do  not  rupture  develop  small  aneurysms  in  their  walls 
at  the  sites  of  the  diseased  media.  Tuberculous  mesarteritis  may 
be  either  of  a  septicsemic  origin  or  by  the  direct  invasion  from  a 
neighbouring  focus. 

Of  the  infections  which  lead  to  dangerous  medial  disease,  syphilis 
stands  in  the  front  rank.  The  frequency  of  syphilitic  mesarteritis 
varies  in  different  countries  and  in  different  cities.  Heller  and  his 
pupils  reported  its  frequent  occurrence  in  Kiel;  Baerthleni  believed 
that  much  the  larger  proportion  of  cases  of  arteriosclerosis  up  to 
middle  life  was  due  to  syphilis    (Munich)  ;   Edgress   found  that 


Etiological  Factors.  73 

syphilitic  arterial  lesions  were  commonest  before  the  age  of  forty- 
six;  while  from  Great  Britain  we  have  not  infrequent  reports  of  the 
occurrence  of  syphilitic  mesarteritis  among  the  soldiers.  In  my 
own  experience  syphilitic  mesarteritis  has  been  among  the  less  fre- 
quent forms,  while  typhoid  and  the  infectious  diseases  of  childhood 
were  the  more  common  causative  agents  of  arterial  lesions  in  early 
life.  Typhoid  is  probably  the  commonest  infectious  disease  of  the 
young  adult  in  the  cities  of  northeastern  America  and  almost 
invariably  the  arteries  of  the  fatal  cases  show  the  early  fatty  and 
degenerative  changes  of  the  intima  along  with  lesions  in  the  media 
of  the  acute  or  productive  type. 

It  has  been  pointed  out  by  several  authors  that  infectious  diseases 
of  childhood  lead  to  arterial  diseases  which  may  play  an  important 
role  in  the  development  of  true  arteriosclerosis  o:^  later  Hfe. 
Simnitsky  working  in  Chiari's  laboratory  found  sclerotic  processes 
of  various  kinds  in  children  who  had  died  of  scarlatina.  He  found 
that  in  48.7  per  cent,  of  the  cases  of  fatal  scarlet  fever,  between  the 
ages  of  two  and  twenty-five,  showed  degenerative  changes  both  in 
the  intima  and  media  but  he  could  find  no  relation  between  the 
intimal  lesions  and  any  condition  in  the  media  or  vasa  vasorum. 

Weisel  confirmed  the  finding  of  Landouzy  and  Siredey,  who 
reported  that  arteriosclerotic  processes  were  prone  to  follow  infec- 
tious diseases.  Weisel  pointed  out  that  in  the  diseases  diphtheria, 
scarlet  fever,  measles,  pneumonia,  influenza  and  typhoid,  although 
no  naked  eye  changes  may  be  observed  in  the  vessels  microscopic 
alterations  and  degenerations  are  commonly  present.  Exactly 
what  relations  these  acute  processes  of  the  infectious  fevers  have  to 
the  later  and  more  chronic  development  of  arteriosclerosis,  these 
authors  do  not  suggest. 

2.  Poisons. — We  knoAv  much  less  about  the  effect  of  poison  upon 
the  human  vascular  system  than  of  infection.  Though  text-books 
persist  in  blaming  lead,  alcohol  and  nicotin  for  certain  changes  in 
the  arteries,  yet  definite  evidence  is  not  forthcoming  to  establish  this. 
Particularly  have  the  observations  of  the  effect  of  lead  and  alcohol 
been  almost  entirely  negative  in  establishing  any  relation  between 
these  substances  and  arteriosclerosis.  It  is  further  to  be  pointed 
out  that  although  the  general  statement  that  lead  and  alcohol  pro- 


74  Arteriosclerosis.    Diseases  of  the  Media. 

duce  arteriosclerosis  is  common,  there  has  never  been  a  definite 
arteriosclerotic  lesion  described  which  was  caused  by  either  of  these 
drugs.  Experiments  have  been  undertaken  on  animals  with  both 
lead  and  alcohol  and  no  arterial  lesions  w^ere  achieved  (Jores). 
This  appears  to  me  to  be  strong  evidence  that  at  the  present  time 
we  must  be  very  guarded  in  crediting  either  of  these  substances  with 
this  severe  charge.  In  the  case  of  nicotin  the  charge  is  somewhat 
different  for  although  in  man  we  have  not  been  able  to  establish  a 
definite  lesion  as  the  result  of  tobacco,  we  have,  however,  in  animals, 
been  able  to  produce  arterial  degenerations  with  both  nicotin  and 
tobacco  smoke.  These  lesions  have  been  medial  degenerations,  of 
the  same  type  as  those  produced  by  adrenalin  (Adler  and  Hensel). 

The  effect  of  nicotin  and  tobacco  is  directly  upon  the  musculature 
of  the  circulatory  system.  Fatty  degeneration  of  the  heart  from 
excess  tobacco  has  been  demonstrated,  and  in  animals  similar 
changes  in  the  musculature  of  the  heart  and  vessels  have  been  noted. 
There  is  besides  this  an  increase  of  blood  pressure  during  the  nicotin 
intoxication,  which  may  also  have  a  bearing  on  the  disease  process. 

We  may  say,  therefore,  that  the  untoward  effect  of  nicotin  and 
tobacco  on  the  arterial  system  appears  quite  definite,  but  that  definite 
evidence  is  lacking  that  alcohol  and  lead  produce  arteriosclerosis. 

That  adrenalin,  barium  chloride,  hydrastin,  digitalin  and  other 
poisons  have  degenerative  effects  on  the  musculature  of  the  arteries, 
has  been  shown  in  animal  experiments,  but  what  bearing  these  ob- 
servations have  on  toxic  arteriosclerosis  in  man  remains  undecided. 

3.  Work. — We  can,  however,  present  a  much  stronger  case  that 
work  produces  arteriosclerosis.  Evidence  has  been  accumulating 
for  many  years,  but  more  particularly  in  the  last  decade,  that  an 
excessive  amount  of  work  thrown  on  the  arteries  will  lead  to 
degenerative  changes.  The  musculature  of  the  vessel  wall  is  sub- 
ject to  fatigue  like  other  muscle  fibres,  and  this  fatigue  results  in 
the  first  place  in  a  loss  of  tone  and  dilatation  of  the  arterial  tube, 
while  if  the  strain  be  continued  the  muscle  fibres  are  lowered  in 
their  vitality.  This  loss  of  vitality  is  evident  in  the  microscopic 
"cloudiness,"  and  a  deposit  of  fat  granules  in  the  substance  of  the 
muscle  fibres.  From  this  condition  the  degeneration  progresses, 
until  finally  the  death  of  the  muscle  elements  leaves  a  much  weak- 


Etiological  Factors.  75 

ened  arterial  wall.  The  commonest  site  of  these  progressive  degen- 
erations of  the  media  is  found  in  the  femoral  artery.  Such  indivi- 
duals whose  occupation  requires  them  to  be  constantly  on  their  feet 
show  the  various  stages  of  degeneration  and  loss  of  the  muscle 
elements  of  the  media,  accompanied  by  multiple  aneurysmal  sacs. 
These  aneurysms  vary  in  size  from  a  bead  to  that  of  a  marble. 

In  a  similar  manner  the  radial,  tibial,  popliteal,  iliac,  uterine  and 
brachial  arteries  show  degenerative  changes,  and  occasionally 
aneurysms,  as  the  result  of  the  intermittent  increased  blood  pressure 
within  them. 

Thayer  and  Fabyan  examined  the  radial  and  other  arteries  from 
a  series  of  cases  which  during  life  had  been  studied  in  the  wards  of 
the  Johns-Hopkins  Hospital.  The  authors  found  that  wherever 
arteries  had  been  subjected  to  strain,  these  vessels  showed  scleroses, 
due  either  to  the  extra  tissue  by  which  the  vessels  had  fortified  them- 
. selves,  or  to  degenerative  processes  in  the  media  (calcification). 
These  authors  state  that  "an  unduly  thickened  radial  at  an  early 
age  may  mean  one  of  two  things :  (i)  the  vessel  has  been  subjected 
to  unusual  and  exceptional  strain  or  (2)  it  is  a  vessel  which,  from 
inherent  weakness,  has  been  unable  to  cope  with  conditions  which 
might  ordinarily  be  regarded  as  normal." 

The  truth  of  these  inferences  respecting  the  effect  of  excessive 
work  on  the  arterial  walls  has  been  demonstrated  experimentally,  as 
I  have  already  reported. 

In  all  these  instances  of  work  arteriosclerosis  there  has  been  an 
external  influence  which  has  caused  the  high  blood  pressure  in  the 
arteries.  The  constant  tramp  of  the  pedestrian  continually  jars  and 
jogs  the  blood  column  in  the  vessels  of  the  legs,  which  is  only 
relieved  by  the  elasticity  of  the  media.  The  daily  use  of  the  right 
arm  in  manual  labor,  and  more  particularly  in  such  work  which 
throws  the  blood  suddenly  backward  and  forward  (as  in  black- 
smithing)  leads  to  hypertrophy  and  later  scleroses  of  the  radial  and 
brachial  arteries.  It  is,  however,  more  difficult  to  gauge  the  effect 
of  mental  labor  on  the  vessels  of  the  brain.  That  there  is  an 
increased  flow  of  blood  to  the  brain  during  mental  activity  is  known, 
but  we  lack  in  this  the  jarring  of  the  blood  stream  on  the  vessel 
walls.     However,  long  continued  mental  strain  with  a  recurring 


76  Arteriosclerosis.    Diseases  of  the  Media. 

high  pressure  is  probably  also  able  to  completely  tire  the  muscle 
fibres  with,  in  extreme  cases,  resulting  degenerative  changes  in  them. 
The  same  is  likely  true  of  the  arteries  of  other  overworked  organs. 

4.  Old  Age. — It  is  perhaps  improper  to  classify  old  age  among 
the  agents  bringing  about  a  diseased  condition  of  any  organ,  but 
what  we  wish  to  imply  is  that  the  continuous  Avear  and  tear  of  the 
system,  even  that  amount  which  takes  place  under  physiological 
conditions,  does  after  a  certain  length  of  time  leave  its  mark  upon 
the  tissues.  The  French  have  spoken  of  this  normal  wear  and  tear 
as  "the  rust  of  life."  In  almost  all  organs  the  senile  changes 
amount  to  disturbance  of  nutrition  with  its  consequences.  Simple 
atrophy  of  the  organs  is  the  earliest  sign  of  senile  changes,  and  in 
the  arteries  this  amounts  to  a  diminution  of  the  media.  Death  of 
cells  need  not  necessarily  be  present  in  simple  atrophy,  but  as  soon 
as  this  does  result  there  is  a  simultaneous  increase  in  the  connective 
tissues.  This  increase  in  connective  tissue  may  only  be  relative, 
but  is  frequently  real.  The  senile  type  of  arteriosclerosis  in  vessels 
of  the  elastic  tissue  type  is  very  definite  and  is  not  to  be  mistaken  for 
any  of  the  other  forms.  Its  mode  of  selecting  that  part  of  the  media 
which  is  most  poorly  nourished  is  characteristic.  I  cannot  agree 
with  Romberg's  designation  of  arteriosclerosis  in  general,  as  an 
"abnutzungs  krankheit."  It  has  been  definitely  shown  that  there 
are  certain  agents  which  bring  about  arteriosclerosis  of  particular 
kinds,  and  when  these  agents  are  infections,  fevers  or  intoxications,  it 
would  be  wrong  to  speak  of  the  arterial  lesions  as  processes  of  wear 
and  tear.  The  term  "abnutzungs  krankheit"  as  regards  arterio- 
sclerosis is  only  applicable  to  that  type  occurring  in  old  age,  and  as 
this  type  presents  such  characteristic  features  from  the  usual 
arteriosclerosis,  I  would  well  recommend  Romberg's  term  for  this 
disease. 

It  has  been  well  established  by  Aschoff  that  the  elastic  fibres  of  an 
artery  undergo  a  change  with  advancing  age.  There  is  a  definite 
increase  in  the  quantity  of  elastic  tissue  from  infancy  to  adult  life, 
and  this  increase  appears  to  be  in  direct  proportion  to  the  increase 
of  pressure  within  the  arteries.  However,  our  knowledge  of  the 
variation  of  the  blood  pressure  at  the  various  ages  of  life  and  in 
the  different  blood  vessels  is  imperfect;  and  until  this  is  deter- 


Etiological  Factors.  77 

mined  definite  statements  cannot  be  made  for  any  particular  artery. 
Aschoff  takes  it,  however,  that  for  every  continuous  increase  of  the 
arterial  tension  there  is  a  parallel  development  of  elastic  fibres. 
This  physiological  development  of  elastic  fibres  is  common  to  all 
persons  up  to  middle  age.  From  this  time  on  the  senile  changes 
in  the  arteries  creep  in,  and  we  can  no  longer  follow  the  changes 
in  individual  tissues,  common  to  all  persons.  Aschoff  finds  that 
there  is  a  senile  arteriosclerosis  localized  to  the  intima  which  con- 
sists of  thickenings  and  degenerations  particularly  noted  at  the 
points  of  bifurcation.  As,  hoAvever,  these  changes  are  not  con- 
stant in  every  person  over  middle  age,  and  as  in  some  cases  of  old 
age  these  intimal  degenerations  are  completely  lacking,  I  am  reluc- 
tant to  regard  these  as  senile  arteriosclerosis.  Rather  than  being 
only  the  result  of  wear  and  tear,  I  believe  these  plaques  at  the 
points  of  division  of  the  arteries  represent  lesions  of  definite  etio- 
logical factors  and  not  senility.  It  is  otherwise  with  the  degener- 
ations of  the  media  which  I  have  above  described  as  senile  arterio- 
sclerosis. These  granular,  fatty  and  calcareous  degenerations  of 
the  muscle  cells,  I  have  found  only  in  senility  in  human  arteries, 
and  have  noted  that  in  all  cases  of  old  age  these  degenerations  are 
to  be  found. 

Interesting  observations  were  made  by  Foster  in  our  laboratory, 
on  the  changes  taking  place  in  the  elastic  tissue  of  the  aorta  in 
advancing  age.  Foster  found  that  there  were  definite  periods  in 
life  when  these  changes  occurred.  The  elastic  fibres  of  the  media 
show  a  gradual  increase  in  their  size  and  number  up  to  the  thirty- 
fifth  year.  With  this  increase  in  the  elastic  tissue,  the  relative 
proportion  of  elastic  fibres  to  muscle  tissues  is  altered  in  favor  of 
the  elastic  laminse.  After  the  thirty-fifth  year  there  is  a  period  of 
quiesence  lasting  for  about  fifteen  years.  During  this  time  no 
definite  changes  occur  in  the  elastic  fibres  save  when  some  intercur- 
rent disease  processes  develop  in  the  vascular  tissues.  The  third 
period  of  life, — from  about  the  fiftieth  year  onward,  is  marked 
by  the  atrophic  changes  of  senescence.  The  muscle  fibres  atrophy 
more  rapidly  than  the  other  tissue  cells,  leading  to  a  relative  scle- 
rosis, and  an  apparent  increase  in  the  elastic  fibres.  Moreover  the 
elastic  tissue  in  itself  shows  the  changes  of  the  decay  of  life.     The 


78  Arteriosclerosis.    Diseases  of  the  Media. 

fibres  no  longer  possess  the  elasticity  of  the  adolescent  structures, 
the  staining  reactions  are  no  longer  uniform  and  the  individual 
fibres  show  rough  and  ragged  borders  in  place  of  the  smooth  un- 
dulating contour  of  the  young  fibres.  The  aortic  wall  in  this  third 
period  may  be  thinner  than  is  usually  seen  in  the  second  period, 
due  to  the  actual  loss  of  muscle  strands  and  lamellae,  with  the  close 
crowding  of  the  elastic  rings. 

It  is  to  be  observed  that  in  the  vessels  of  old  age  the  relative 
increase  in  the  elastic  tissue  of  the  artery,  even  in  the  absence  of  an 
actual  connective  tissue  increase,  leads  to  a  less  elastic  wall.  The 
two  factors,  loss  of  muscle  tissue  and  alteration  in  the  nature  of 
the  elastic  fibres,  are  responsible  for  this. 


ANEURYS^IS  AND  MEDIAL  DISEASES. 

A  brief  reference  must  be  made  of  the  association  of  medial 
diseases  with  aneurysms. 

Although  there  have  been  a  great  number  of  reports  in  the  liter- 
ature concerning  aneurysm,  there  is  to  the  present  day  no  common 
opinion  concerning  their  etiology.  On  the  contrary,  like  arterio- 
sclerosis, the  views  expressed  on  the  subject  of  aneurysms  have 
been  so  divergent  and  manifold  that  difficulty  is  experienced  in 
following  the  history  of  this  subject,  and  of  giving  proper  credit  to 
the  observations  of  the  older  writers. 

To  Vesalius  we  are  indebted  for  the  first  recognition  of  aneu- 
rysm, but  little  information  is  obtained  of  their  nature  from  his 
descriptions.  His  contemporary,  Fernelius,  offered  the  first  ex- 
planation for  the  condition,  which  was  accepted  for  the  time.  He 
taught  that  every  aneurysm  consisted  of  a  dilatation  of  all  the 
arterial  coats,  and  that  syphilis  was  the  cause.  It  was  soon  found 
that  his  definition  Avas  too  narrow,  and  a  division  was  made  into 
true  and  false  aneurysms. 

Various  descriptions  of  aneurysm  of  different  arteries  are  to  be 
found  in  the  writings  of  the  masters- of  the  early  eighteenth  cen- 
tury  (Morgagni,  Severinus,  Guattani,  Verbrugge,  Lancisi).  By 
true  aneurysm  Lancisi  referred  to  those  conditions  in  which  the 
arterial  wall  was  weakened  and  dilated,  while  a  false  aneurysm 
was  a  dilated  artery  as  the  result  of  external  injury.  Interesting 
it  is  too,  that  these  observers  recognized  an  association  of  syphilis 
to  aneurysm,  but  expressed  an  opinion  that  possibly  it  was  the 
mercurial  treatment  and  not  syphilis  which  acted  upon  the  vessels. 

It  will  be  appreciated  that  the  observations  made  upon  the  ap- 
pearance of  aneurysm,  were  isolated  to  the  cases  coming  into  the 
anatomist's  hands.  Commendable  are,  too,  the  accurate  macro- 
scopic descriptions  which  they  haA^e  handed  down  to  us.  On  the 
other  hand,  the  want  of  knowledge  concerning  structural  changes 
in  the  arteries  led  to  much  speculation  and  to  many  theories. 

At  the  beginning  of  the  nineteenth   centur}^   Scarpa   described 

79 


80  Arteriosclerosis.    Diseases  of  the  Media. 

aneurysm  as  a  rupture  of  an  artery  produced  either  by  trauma  or 
by  a  "  degenerazione  steatomatosa  ''  or  through  ulceration,  with 
an  effusion  of  blood  into  the  surrounding  tissues.  He  further 
classified  these  lesions,  "  spontaneous "  when  the  aneurysm  had 
resulted  from  disease  in  the  wall,  while  all  the  traumatic  aneurysms 
of  the  arteries  he  called  "  spurious."  Scarpa  has  the  distinction 
however  of  first  stating  that  no  aneurysms  arise  without  a  disease 
or  abnormal  condition  of  the  media.  Monro,  on  the  other  hand, 
claimed  that  the  term  aneurysm  was  applied  to  localized  or  diffuse 
stretching  of  all  of  the  arterial  coats,  while  false  aneurysm  referred 
to  the  blood  sac  formed  outside  of  the  artery  but  still  in  communica- 
tion with  the  arterial  channel. 

Scarpa  in  1804,  pointed  out  that  dilatations  of  the  arteries  were 
associated  with  a  peculiar  and  distinct  disease  of  their  walls,  but  not 
until  181 5  was  it  shown  by  Krisig  and  also  Hodgson  that  these 
arterial  diseases  were  of  an  inflammatory  nature.  More  particu- 
larly was  it  shown  by  Krisig  that  this  inflammation  was  present  in 
almost  every  form  of  aneurysm  and  that  possible  ulcerations  were 
secondary  processes  in  the  condition.  A  series  of  observations 
were  then  reported  by  Bruns,  Guthrie,  Lobstein,  Bonders  and  Jan- 
sen,  most  of  whom  supported  the  inflammatory  origin  of  aneurysm. 
Guthrie  laid  stress  upon  chronic  irritation  or  inflammation  as  the 
factors  leading  to  alterations  in  the  arteries.  "  The  first  and 
simplest  change,"  he  says,  "  is  a  loss  of  the  elasticity  natural  -to 
them,  which  may  lead  to  a  state  of  dilatation  without  abrasion 
or  rupture  of  any  of  the  component  parts  of  the  artery,  although 
sometimes  accompanied  by  a  general  diminution  of  substance  of  the 
middle  coat."  Guthrie  studied  many  of  the  specimens  collected 
by  Hunter,  and  it  is  of  interest  that  he  recognized  a  primary  disease 
occurring  in  the  media  having  no  relation  to  changes  taking  place 
in  the  intima. 

Rokitansky  on  the  other  hand  believed  that  the  mechanical  func- 
tional overstrain  of  the  arteries  was  a  predisposing  factor  for 
endarteritis,  and  also  for  the  development  of  aneurysm.  He  con- 
tended that  the  portion  of  the  aorta  which  was  called  upon  to  do 
the  greatest  amount  of  work  showed  the  development  of  aneurysm 
most  frequently. 


Aneurysms  and  Medial  Diseases.  81 

Traube  had  supported  the  inflammatory  theory  of  aneurysm  and 
believed  that  the  white  blood  cells  were  attracted  from  the  blood 
stream  through  the  endothelium,  and  formed  there  the  white  scle- 
rotic plaques  of  intimal  thickening.  The  result  of  this  superficial 
inflammatory  reaction  led  to  a  weakening  of  the  wall.  Koester 
agreed  with  this  contention,  but  thought  that  the  degeneration  of 
the  intima  was  primary  and  the  invasion  of  leucocytes  was  a  secon- 
dary condition. 

These  theories  were  strongly  opposed  by  Virchow.  In  the  first 
place  he  held  that  endarteritis  was  a  true  inflammation  of  the  intima 
resulting  from  a  given  irritation.  Such  inflammation  could  arise 
from  various  causes  and  possibly  through  the  action  of  the  blood 
upon  small  erosions  in  the  intima.  From  his  observations  Virchow 
came  to  recognize  differences  between  lesions  resulting  from  prolif- 
erative changes  in  the  intima,  and  the  primary  fatty  degenerations 
of  this  coat.  He  also  differentiated  the  minute  changes  occurring 
in  the  media  either  with  or  without  intimal  diseases.  In  these 
latter  states  he  found  that  aneurysms  were  most  prone  to  develop. 

Still  other  views  were  brought  forward,  v.  Recklinghausen  was 
of  the  opinion  that  the  primary  disease  preceding  aneurysm  was 
a  mechanical  overdistension  of  the  vessel  leading  to  rupture  of  the 
elastic  fibres  of  the  vessel  coat.  Helmstaedter  too  ascribed  the 
main  changes  leading  to  aneurysm  as  destruction  of  the  media  and 
more  particularly  the  elastic  tissue.  More  direct  evidence  was  soon 
brought  forward  by  Trompetter  and  Auerbach  that  many  of  the 
aneurysms  of  the  aorta  were  associated  with  a  mesarteritis  and 
that  in  some  cases  little  or  no  damage  was  to  be  found  in  the  intima. 

Some  years  later  Koester  altered  his  original  view  and  expressed 
his  opinion  that  arterial  disease  was  commonly  associated  with  an 
inflammatory  infiltration  about  the  vasa  vasorum.  Koester  in  fact 
now  believed  that  this  was  an  essential  condition  in  arteriosclerosis. 
Thus  we  find  Koester  teaching  that  every  endarteritis  had  a  mes- 
arteritis preceding  it.  Later  on  we  find  Kraft  agreeing  with  but 
modifying  Koester's  view.  Every  inflammation  of  the  arteries,  he 
said,  attacked  the  media  and  did  not  advance  into  the  intima.  He 
believed,  however,  that  aneurysms  were  the  result  of  a  diffuse  in- 


82 


Arteriosclerosis.    Diseases  of  the  Media. 


flammation  in  the  muscular  coat  which  advanced  to  it  from  the 
adventitia  by  way  of  its  nutrient  vessels. 

Almost  all  the  authors  were  agreed  on  the  presence  of  an  ante- 
cedent disease,  in  the  arterial  coats,  to  aneurj^sm,  yet  these  same 
authors  expressed  some  doubt  in  the  direct  relationship  of  arterio- 
sclerosis to  aneur}^sm.  The  chief  stumbling  block  lay  in  the  fact 
that  arteriosclerosis  was  a  disease  which  progressed  with  advancing 
years  while  aneurysm  was  most  frequent  between  the  ages  of  thirty 
and  forty,  and  did  not  increase  in  frequency  in  old  age.  Crisp 
and  Lebert,  give  very  comprehensive  tables  indicating  the  frequency 
of  aneurysm  at  the  various  periods  of  life.  A  similar  table  is  also 
given  by  Lisfranc. 


Age. 

1      I-IO. 

10-20. 

20-30. 

30-40. 

40-50. 

50-60. 

60-70. 

70-80. 

Cases. 

Crisp 

Lisfranc 

Lebert 

I 
I 

5 

4 
5 

71 
17 

42 

31 

198 
29 
80 
81 

129 
37 
75 
69 

65 
17 
70 

24 

25 

3 

35 

20 

8 

3 
0 
6 

502 
120 

318 
241 

Lidell 

2 

8 

Total 

36 

161 

388 

310 

176 

83 

17 

1,181 

In  opposition  to  these  figures.  Richter  finds  that  in  a  series  of 
366  cases  of  aneurysms  collected  by  him  the  age  incidence  of 
arteriosclerosis  and  aneurvsm  is  not  so  dissimilar. 


10-20  years. 

20-30. 

30-40. 

40-50. 

50-60. 

'       60-70. 

'       70-80. 

5 

49 

217 

269 

133 

52 

II 

Peterson-Borstell  found  that  in  2,982  autopsies  64.7  per  cent. 
of  the  cases  between  the  ages  of  fifty  and  eighty  had  endarteritis, 
while  95  per  cent,  of  the  cases  above  eighty  years  showed  evidence 
of  the  disease. 

In  the  discussion  of  the  relationship  of  endarteritis  to  aneurysm 
Birch-Hirschfeld  emphasized  the  frequency  of  the  former  condi- 
tion after  middle  life,  while  aneurysms  are  relatively  few  at  this 
age.  In  this  point  alone,  he  says,  there  is  evidence  that  the  ordi- 
nary endarteritis  is  not  directly  associated  with  dilatation  of  the 
vessel. 

LaAvson,  in  England,  too  recognized  the  infrequency  of  aneu- 


Aneurysms  and  Medial  Diseases.  8S 

rysms  with  atheromatous  processes  in  the  arteries.  His  observa- 
tions were  chiefly  among  the  soldiers  at  Aldershot,  and  he  says  that 
"  aneurysm,  as  I  have  met  with  it  among  soldiers,  seems  frequently 
to  exist  quite  independent  of  that  form  of  disease  of  the  arteries, 
and  the  destruction  of  large  portions,  of  even  the  whole  three  coats 
may  take  place  by  an  acute  process  and  without  a  trace  of  atheroma 
in  the  neighborhood"  (Osier).  Aneurysm  occurs  at  the  Kiel 
Pathological  Laboratory  in  the  frequency  of  one  in  two  hundred 
.utopsies   (Kroeger). 

There  have  been  a  few  cases  reported  in  literature  in  which 
aneurysm  was  noted  in  the  arteries  which  otherwise  appeared  quite 
healthy.  It  is  probable  that  in  these  cases  the  vessel  was  locally 
diseased  or  that  minute  histological  examinations  were  not  under- 
taken to  demonstrate  conditions  which  could  not  be  recognized 
with  the  naked  eye.  Such  remarkable  specimens,  however,  led 
some  to  support  the  mechanical  theory  of  aneurysms. 

With  a  development  of  better  technique,  many  observers  have 
busied  themselves  in  demonstrating  one  or  more  causative  factors 
in  human  aneurysms  or  in  reproducing  the  lesions  in  animals. 

This  brings  us  to  fairly  modern  times,  when  the  controversy  re- 
specting aneurysm  became  centered  about  its  relation  to  syphilis. 
But  we  must  not  fail  to  recognize  that  the  history  of  syphilitic 
arterial  disease  takes  us  a  long  way  i>ack  in  the  literature.  Am- 
broise  Pare,  although  not  the  first  to  observe  the  occurrence  of 
certain  arterial  diseases  and  aneurysms  after  syphilis,  was  neverthe- 
less the  strongest  exponent  of  their  relation,  in  the  middle  of  the 
sixteenth  century.  Similar  observations  were  later  made  by  Lan- 
cisi,  Severinus,  Morgagni  and  others,  who,  although  observing  the 
relationship  of  syphilis  to  aneurysm,  did  not  appear  to  have  decided 
whether  the  result  was  from  the  French  disease  or  from  the  mer- 
curial treatment. 

For  some  years  little  stress  was  laid  upon  these  findings. 
Guthrie  in  1830,  denied  the  association  of  syphilis  with  aneurysm. 
He  recognized  the  frequency  of  aneurysm  in  the  ascending  arch  of 
the  aorta  in  which  he  found  all  the  tunics  more  or  less  retained. 
These  aneurysms  he  spoke  of  as  preternatural  dilatations.  He 
says,  "  preternatural  dilatations  are  most  frequently  met  with  in  the 


84  Arteriosclerosis.    Diseases  of  the  Media. 

ascending  aorta  and  at  the  arch;  they  have  been  less  often  observed 
in  the  aorta  descendens.  They  are  not  uncommon  in  the  arteries 
within  the  skull."  This  author  makes  a  distinction  between  preter- 
natural dilatations  "  when  an  arter}'-  is  enlarged  in  its  whole  cir- 
cumference," and  aneurysms  "  when  the  tumor  seems  to  grow  from 
one  side  or  part  of  the  artery  alone."  In  aneurysms  Guthrie  found 
that  the  wall  of  the  sac  not  infrequently  showed  inflammatory  con- 
ditions which  he  believed  were  due  to  the  action  of  the  poorly  cir- 
culating blood,  in  the  sac,  upon  the  arterial  wall.  It  is  not  improb- 
able that  Guthrie's  preternatural  dilatations  or  fusiform  aneurysms 
were  a  mild  and  more  diffuse  syphilitic  lesion  of  the  aorta. 

In  1862,  Aitken,  in  England,  found  among  twenty-six  cases  of 
syphilis,  seventeen  aneurysms  of  the  aorta.  In  1862,  Davidson 
reported  these  and  other  cases  in  the  Army  Medical  Reports  of 
England.  These  reports  of  syphilitic  aneurysm  were  followed 
by  others  in  England,  which,  however,  are  scattered  through  a 
rather  inaccessible  literature. 

The  frequency  of  aneurysm  in  the  army  was  a  subject  of  com- 
ment in  the  middle  of  the  last  century.  The  majority  of  reported 
cases  of  that  time  came  from  England,  until  continental  authors 
spoke  of  "England,  the  land  of  aneurysms"  (Spleidt).  Billroth 
in  his  work  on  pathology  stated  that  "  the  occurrence  of  aneurysm 
had  a  remarkable  distribution  in  Europe.  In  Germany  aneurysms 
are  uncommon,  as  they  also  are  in  Belgium,  they  are  more  frequent 
in  France  and  Italy,  and  most  commonly  found  in  England.  It 
is  difficult  to  give  definite  reasons  for  this,  but  it  is  a  fact  that 
arterial  diseases  along  with  rheumatism  and  gout  are  more  fre- 
quent in  England  than  in  any  of  the  other  European  countries." 

This  variation  in  the  incidence  of  aneurysm  in  different  coun- 
tries is  well  illustrated  in  the  statistics  collected  by  Osier.  From 
his  figures  it  is  found  that  at  the  Johns-Hopkins  Hospital,  aneu- 
rysm is  more  common  than  in  Germany  or  even  England. 

Important  observations  were  made  by  Francis  Welch  in  1875. 
He  had  the  opportunity  of  studying  thirty-four  cases  of  aortic 
aneurysm,  occurring  in  the  army,  over  half  of  which  had  had  a 
definite  attack  of  syphilis.  Welch  is  the  first  to  give  us  a  full 
account  of  the  appearance  of  syphiHtic  lesions  in  the  aorta,  and 


Aneurysms  and  Medial  Diseases.  85 

to  give  the  points  of  differentiation  from  the  other  arteriosclerotic 
processes.  He  pointed  out  that  ^Yhere  fatty  degeneration  occurred 
in  a  syphilitic  aortitis,  it  was  an  associated  and  not  a  primary 
lesion. 

As  Osier  points  out,  it  was  chiefly  the  army  physicians  of  Eng- 
land who  were  convinced  of  the  immense  importance  of  syphilis 
as  the  prime  factor  in  aortic  aneurysm. 

At  the  time  of  publication,  Welch's  contentions  received  consid- 
erable criticism  from  others  than  the  army  medical  physicians  in 
England,  and  the  general  controversy  on  the  question  of  the  etiol- 
ogy of  aneurysm  was  opened  with  renewed  interest.  It  may  be 
said  that  Welch's  observations  on  the  appearance  and  differentia- 
tion of  syphilitic  aortitis  are  the  beginning  of  a  new  era  in  our 
knowledge  of  syphilitic  disease  of  the  arteries.  The  fundamental 
principles  enunciated  by  Welch,  associating  aneurysm  with  syphilis, 
have  been  little  altered  today. 

In  Norway,  we  find  similar  controversies  respecting  the  associa- 
tion of  syphilis  with  arterial  disease.  Heiberg  in  1876  pointed  out 
that  probably  the  greater  proportion  of  chronic  inflammation  of 
the  arteries  (?  aorta)  was  the  result  of  syphilis,  and  his  opinions 
were  later  supported  by  his  countrymen  ]\Ialmsten  and  Rasch.  In 
France,  too,  little  support  was  given  to  these  new  views.  How- 
ever, in  1879,  Vallin  reported  a  case  oi  aortic  aneurysm  following  a 
definite  attack  of  syphilis,  and  these  observations  were  soon  fol- 
lowed by  many  others.  A  similar  scepticism  prevailed  in  Germany, 
until  the  clinicians,  Gehardt,  Quincke,  Fraenkel,  and  others,  ob- 
served the  association  of  these  diseases  in  their  patients.  The 
German  pathologists  at  first  gave  but  a  passive  affirmation  to  these 
findings,  but  later  when  more  acute  attention  was  directed  to  the 
subject  it  was  demonstrated  that  a  more  than  casual  relationship 
existed  between  syphilis  and  aneurysm. 

To  Heller  and  his  pupils  we  owe  the  greatest  indebtedness  for 
the  definite  differentiation  of  aortitis  syphilitica  from  chronic  en- 
darteritis. Since  Heller  first,  through  his  pupil  Doehle,  directed 
attention  to  the  importance  of  syphilitic  aortitis,  he  has  repeatedly 
brought  to  our  notice  cases  of  aneurysm  associated  with  syphilis  of 
the  aorta.     The  collected  reports  from  the  Kiel  school  give  very 


86  Arteriosclerosis.    Diseases  of  the  Media. 

complete  information  respecting  the  frequency,  site  and  syphilitic 
nature  of  aneurysms. 

Recklinghausen  believed  that  aneurysm  of  the  aorta  developed 
as  a  result  of  a  primary  rupture  of  the  elastic  fibres.  This  process 
was  more  fully  described  by  his  pupil  Helmstaedter,  who  found  in 
several  cases  of  aneurysm  of  the  aorta,  in  which  the  intima  was 
comparatively  normal  but  in  places  retracted,  that  peculiar  areas 
occurred  in  the  media  in  which  the  elastic  fibres  had  disappeared 
or  appeared  to  have  ruptured.  Into  these  areas  of  destruction  a 
new  connective  tissue  developed  but  formed  a  weaker  wall  than 
normal. 

One  cannot  but  be  struck  by  the  similarity  of  the  descriptions  of 
Helmstaedter  with  the  picture  of  syphilitic  mesarteritis. 

Heubner  was  one  of  the  early  investigators  who  indicated  that 
syphilis  of  the  arteries  was  of  a  specific  nature.  From  his  studies, 
however,  he  was  led  to  conclude  that  the  disease  began  in  the  endo- 
thelium and  that  the  media  and  adventitia  were  only  later  involved. 

Chiari  too  points  out  the  points  of  differentiation  between  the 
ordinary  sclerotic  processes  in  the  aorta,  and  those  of  syphilis. 
The  latter,  he  said,  formed  a  class  of  chronic  mesarteritis  which 
was  distinct  and  could  be  separated  from  other  forms  of  chronic 
mesaortitis.  His  work  has  shown  that  syphilis  of  the  aorta  is  a 
destructive  disease  of  the  media  which  advances  to  it  from  the 
adventitia. 

It  is  worthy  of  note  that  there  have  been  not  a  few  cases  of  aneu- 
rysm reported  associated  with  tabes  dorsalis  (Berger  and  Rosen- 
bach,  Euslin,  Molt,  Halpern  and  others). 

In  the  statistics  on  the  association  of  syphilis  and  aneurysm 
there  are  some  interesting  data.  Heller  pointed  out  that  he  had 
found  syphilitic  aortitis  in  cases  where  syphilis  was  otherwise  not 
recognizable  in  the  body,  while  on  the  other  hand,  he  found  that 
some  individuals  who  had  had  definite  and  severe  attacks  of 
syphilis,  had  not  shown  any  recognizable  changes  in  the  arteries. 
Thus  the  occurrence  of  the  arterial  changes  in  syphilis  varies  con-  . 
siderably.  Aitken  found  aortic  changes  in  68  per  cent,  of  syphi- 
litics;  Welch  found  syphilitic  disease  of  the  aorta  in  46.1  per  cent., 
while  Henderson  demonstrated  lues  in  62.5  per  cent,  of  aortic  aneu- 


Aneurysms  and  Medial  Diseases.  87 

rysms.  The  history  of  the  individual  cases  of  aneurysm  is  also 
interesting  in  that  the  reports  indicate  that  aneurysm  may  develop 
from  one  (Moore)  to  thirty-three  (Malecot)  years  after  the 
infection. 

The  distribution  of  aneurysm  of  the  aorta  follows  the  frequency 
of  syphilis  in  the  various  parts  of  this  artery.  Thus  as  it  has  been 
repeatedly  shown  that  syphilis  has  a  predilection  for  the  ascending 
limb  and  arch  of  the  aorta  so  aneurysm  too  is  more  frequent  in 
these  portions.  Of  forty-eight  aortic  aneurysms  examined  at  the 
Pathological  Institute  at  Kiel  (from  1872  to  1899),  thirty-eight 
were  males  and  ten  females.  The  average  age  was  52  years,  the 
youngest  being  25,  the  oldest  83  years.  The  greater  number,  27, 
occurred  in  the  ascending  aorta,  11  in  the  descending,  10  in  the 
arch.  In  one  case  an  aneurysm  was  present  both  in  the  ascending 
and  in  the  descending  aorta  (Kroeger). 

If  we  now  sum  up  the  points  associating  syphilis  with  aneurysm, 
we  find  that  syphilis  is  prone  to  attack  the  ascending  aorta  by  a 
mesarteritis  whose  prime  feature  is  a  destruction  of  the  essential 
tissues  of  this  coat.  The  fibrosis  in  the  wall  along  with  the  not 
unusual  extensive  endarteritis  are  secondary  processes.  With  the 
media  destroyed  the  artery  is  much  weakened  leading  to  dilatations 
of  various  degrees,  or  even  rupture. 

It  is  only  with  the  appreciation  that  the  media  is  the  mainstay 
of  an  artery,  that  the  full  bearing  of  the  importance  of  syphilitic 
arteritis  is  seen.  Today  we  lay  it  down  as  a  law  that  aneurysms 
can  only  result  when  the  media  is  zveakened,  and  do  not  result  from 
any  disease  process  isolated  to  the  intima  or  adventitia.  Hence, 
too,  it  at  once  becomes  evident  how  important  are  the  diseases  of 
the  media. 

In  discussing  the  question  of  aneurysm  in  general  we  must 
recognize  the  occurrence  of  arterial  dilatations  from  causes  other 
than  syphilis.  The  greater  frequency  of  syphilitic  aneurysm  in  the 
aorta  serves  as  no  guide  to  the  number  of  cases  of  aneurysm  due 
to  syphilis  in  the  other  arteries.  The  peripheral  arterial  system  is 
much  more  exposed  to  direct  injuries  which  damage  and  weaken 
the  arterial  wall,  so  that  aneurysm  results,  than  the  aorta.  Gun- 
shot and  stab  w^ounds  are  among-  the  more  common  of  these  in- 


88  Arteriosclerosis.    Diseases  of  the  Media. 

juries.  Saigo  reports  the  occurrence  of  many  traumatic  aneurysms 
during  the  Russian-Japanese  War,  and  he  beHeves  that  their  great 
frequency  was  the  result  of  modern  ammunition.  These  aneurysms 
developed  from  two  to  five  weeks  after  the  injury  and  were  com- 
monest in  the  upper  arm  and  thigh. 

Again,  as  we  have  pointed  out  above,  of  the  ordinary  sclerotic 
processes  arising  in  the  arterial  system  the  medial  scleroses  are  in 
much  greater  proportion  in  the  peripheral  vessels  than  in  the  aorta, 
and  further  these  medial  scleroses  of  the  peripheral  system  are 
more  common  than  the  affections  of  the  intima  of  the  same  vessels. 
Moreover  it  is  to  be  noted  that  these  medial  scleroses  develop  from 
varied  causes  and  are  to  be  found  of  different  grades  of  intensity 
in  all  individuals  over  fifty  years.  We  would  not  be  surprised 
therefore,  to  find  aneurysmal  pouchings  in  the  peripheral  arteries 
in  many  individuals  beyond  middle  life.  In  my  own  experience 
this  has  been  a  common  finding  when  looked  for.  Particularly 
easy  is  its  demonstration  in  the  femoral  and  iliac  arteries  where 
transverse  pouches  and  sacculations  are  so  often  present.  Often 
these  pouches  appear  multiple,  and  lie  in  parallel  rows  across  the 
artery.  As  I  have  indicated  elsewhere,  these  pouches  are  not  so 
prominent  during  life  when  the  blood  pressure  obliterates  the  still 
elastic  and  less  involved  ridges  between  these  aneurysms.  It  is  to 
be  appreciated  that  during  the  development  of  these  small  saccula- 
tions the  degenerating  media  becomes  sclerosed  and  calcified  so 
that  the  pouch  forms  a  small  rigid  cavity,  fully  dilated  by  the  blood 
pressure.  After  death  with  the  release  of  the  internal  pressure 
the  more  healthy  portions  of  arterial  wall  around  the  sac  contract, 
exaggerating  the  depth  of  the  cavity. 

Although  the  frequency  of  peripheral  aneurysms  of  the  extrem- 
ities is  relatively  great,  their  importance  is  very  much  less  than  that 
of  the  aorta.  The  former  are  as  a  rule  self  limited  and  do  not 
progress  beyond  the  shallow  cuppings  of  the  wall.  On  an  average 
the  peripheral  aneurysmal  pouches  are  present  in  one  out  of  every 
three  individuals  over  fifty  years.  Although  these  aneurysms  of 
the  peripheral  arteries  are  most  often  found  in  the  vessels  of  the 
extremities,  they  are  also  observed  in  the  splenic,  mesenteric,  verte- 
bral and  cerebral  arteries. 


Aneurysms  and  Medial  Diseases.  89 

Another  type  of  arterial  disease  leading  to  aneurysm  must  be 
noted.  Endarteritis  chronica  deformans  with  atheroma  develop- 
ing in  a  small  artery  has  a  much  greater  significance  for  the  devel- 
opment of  aneurysm  in  the  small  arteries  than  in  the  aorta.  It  is 
not  so  many  years  since  pathologists  expressed  the  view  that  aortic 
aneurysms  were  commonly  the  result  of  endarteritis  (Virchow, 
Rindfleisch,  Foerster  and  others).  This  today  we  can  support 
only  for  a  particular  group  of  vessels. 

It  has  been  shown  above  that  the  frequency  of  aortic  aneurysm 
occurs  between  the  ages  of  thirty  to  fifty,  while  the  development 
of  endarteritis  increases  from  this  age  onward.  It  is  to  be  as- 
sumed, therefore,  that  in  the  aorta,  endarteritis  has  less  signifi- 
cance in  the  production  of  aneurysm  than  other  causes. 

We  are  familiar  Avith  the  nodular  atheromatous  processes  occur- 
ring in  the  cerebral  and  coronary  arteries,  and  we  are  frequently 
astounded  at  the  enormous  pearly  plaques  that  develop  in  these 
vessels,  almost  bringing  about  occlusion  of  the  lumen.  A  similar 
sized  plaque  in  the  aorta  would  cause  little  interference  or  injury. 
In  the  small  arteries,  however,  degenerative  changes  of  atheroma- 
tous softening  develop  beneath  the  endothelial  overgrowth.  This 
atheroma  is  not  confined  to  the  intima  but  at  times  also  invades  the 
media,  which  if  deeply  involved  weakens  the  staying  power  of  the 
wall.  At  other  times  the  endarteritic  plaque  does  not  itself  enter 
the  media,  but  by  its  growth  presses  upon  the  tissues  to  such  a 
degree  that  the  coat  is  thinned  and  weakened.  This  pressure 
atrophy  of  the  media  does  allow  some  giving  away  of  the  artery 
with  an  irregular  outline  of  its  lumen.  It  is  a  common  observation 
that  the  endarteritic  plaque  rests  very  looseh'  upon  the  underlying 
media,  so  loosely,  in  fact,  that  it  falls  out  during  cutting.  These 
small  arteries  with  extensive  chronic  endarteritis  form  tortuous 
and  irregular  cylinders,  in  whose  walls  aneurysmal  pouches  are 
evident.  These  lesions  are  not  of  syphilitic  origin  and  are,  at  times, 
seen  in  a  single  system  of  vessels  (cerebral,  coronary,  mesenteric), 
while  the  aorta  is  little  or  not  at  all  involved. 

Richter  was  positive  that  hard  manual  work  which  was  one  of 
the  causes  of  arteriosclerosis  was  also  the  most  important  factor 
in  aneurysm.     According  to  him,  aneurysm  and  particularly  of  the 


90  Arteriosclerosis.     Diseases  of  the  Media. 

aorta  was  a  disease  associated  with  the  working  class,  and  was 
directly  related  to  excessive  muscular  activity.  It  is  undoubted 
that  muscular  exertion  leads  to  a  greater  work  on  the  part  of  the 
arterial  system,  and  it  has  been  shown,  that  in  as  far  as  the  human 
peripheral  arteries  are  concerned,  a  sclerosis  develops  in  the  media 
of  these  vessels ;  that  endarteritis  develops  in  association  with  hard 
work  also  seems  undoubted,  but  the  process  is  probably  one  sec- 
ondary to  fatty  degeneration  of  the  deeper  intima,  particularly  the 
musculo-elastic  layer, 

Goetz  believed  that  for  aneurysms,  other  than  those  that  devel- 
oped from  acute  infections,  atheroma  was  an  important  factor. 
Manning,  v.  Leyden  and  Klemperer  held  similar  views  but  thought 
that  for  the  development  of  aneurysm  from  an  atheromatous  proc- 
ess, a  trauma  in  the  nature  of  a  severe  blow  or  concussion  must 
accompany  it. 

In  1898,  Manning  reported  four  cases  of  aneurysm  of  the  aorta 
which  he  believed  were  of  endarteritic  origin.  Two  of  these  were 
saccular  aneurysms,  in  the  ascending  aorta,  one  was  fusiform  and 
in  the  descending  aorta,  and  the  fourth  was  a  dissecting  aneurysm. 
From  his  descriptions  of  the  first  two  cases  and  with  our  present 
day  knowledge  of  aneurysms,  we  are  inclined  to  suspect  these  were 
associated  with  a  syphilitic  process. 

Koester  was  a  strong  opponent  to  the  view  that  aneurysm  of  the 
aorta  developed  in  consequence  to  endarteritis.  In  the  development 
of  aneurysm  of  the  aorta  there  need  not  be  a  progressive  degenera- 
tion of  the  arterial  wall,  for  aneurysms  occur  in  areas  of  fibrosis  of 
a  former  medial  destruction.  In  syphilitic  mesaortitis  the  process 
is  one  of  chronic  inflammation  in  which  the  loss  of  medial  tissues  is 
to  some  extent  replaced,  step  by  step,  by  new  fibrous  tissue. 
Although  this  new  tissue  is  reparative  in  character,  it  is  far  from 
being  a  tissue  of  the  same  elasticity  and  strength  as  the  normal 
arterial  wall.  With  each  pulsation,  brought  to  bear  upon  this  scar 
tissue,  there  is  a  slight  giving  way  in  the  connective  tissue  fibres, 
which  if  there  is  not  a  s.ufficient  quantity  of  muscular  and  elastic 
tissue  to  restore  the  original  length,  remain  permanently  stretched. 
This  yielding  of  the  connective  tissue  areas  in  the  arteries  leads  to 
the  production  of  aneurysms. 


Aneurysms  and  Medial  Diseases.  91 

This  too  accounts  for  the  frequency  of  aneurysm  in  those  cases  of 
syphilitic  mesarteritis,  where  the  arterial  wall  is  actually  thickened 
by  scar  tissue. 

It  has  been  shown  by  Poletebnow  that  the  arterial  wall  when 
sclerosed  becomes  less  elastic  and  at  the  same  time  more  resistant 
to  a  given  tension.  Examining  two  strips  of  aorta  each  7.5  cm. 
long,  and  taken,  one  from  a  young  and  healthy  individual,  the 
other  from  a  much  sclerosed  artery,  he  found  that  the  former 
allowed  a  stretching  to  16.5  cm.  while  the  diseased  vessel  only 
lengthened  to  9.9  cm.  by  a  weight  of  1000  grams. 

Similar  experiments  were  carried  out  by  O.  Israel,  who  used 
strips  of  aorta  5  cm.  long  and  5  mm.  wide  with  a  constant  weight 
of  75  grams.  The  aortic  strip  of  an  alcoholic  lengthened  to  6.03 
cm.;  a  nephritic  to  6.471  cm.;  a  normal  adult  to  6.95;  and  of  a 
chlorotic  individual  to  7.422  cm.  From  his  observations  he  con- 
cluded that  the  arteries  lose  in  their  elasticity  with  advancing 
arteriosclerosis. 

Luck,  a  pupil  of  Thoma,  observed  that  at  the  beginning  of  the 
arteriosclerotic  process  the  artery  was  more  readily  dilated,  while  as 
the  process  advanced  the  arterial  walls  became  rigid  and  did  not 
react  as  readily  to  varying  pressures.  This  primary  weakening  of 
the  artery  is  a  result  of  nutritional  disturbances,  which  gives  evi- 
dence of  undue  stretching  before  microscopic  changes  are  evident. 
Similar  results  were  obtained  by  Lunz  who  demonstrated  experi- 
mentally that  phosphorus,  lead  and  mercury  intoxications  reduced 
the  resisting  powers  of  the  arterial  wall. 

These  results  find  full  agreement  with  our  own  observations,  and 
have  their  explanation  in  the  altered  condition  of  the  media.  We 
cannot  however  apply  the  facts  of  these  experiments  directly  to 
the  question  of  aneurysm.  Namely  in  demonstrating  the  lessened 
elasticity  of  the  aortic  wall  in  arteriosclerosis,  as  Polotebnow  and 
Israel  have  done,  we  are  not  demonstrating  a  condition  of  greater 
strength  or  resistance  to  intermittent  pressure  and  pulsations.  If 
we  have  in  such  a  sclerotic  artery  a  greater  abundance  of  fibrous 
tissue,  this  tissue  will  be  less  elastic  than  a  normal  vessel,  but  on 
the  very  fact  of  its  diminished  elasticity  this  tissue  when  stretched, 
no  matter  how  little,  does  not  return  to  its  original  length.     Its 


92  Arteriosclerosis.    Diseases  of  the  Media. 

very  condition  of  lessened  elasticity  favors  aneurysm  or  at  least 
diffuse  dilatation. 

Not  alone  is  this  true  for  fibroses  of  the  arterial  wall.  Any 
conditions  which  tend  to  set  aside  the  inherent  elastic  powers  of 
the  muscle  fibres  and  elastic  tissue  will  at  the  same  time  favor  the 
process  of  dilatation  of  this  vessel.  Manchot,  Weisermann  and 
Newmann  Helmstaedter,  Zwingmann  and  others  believed  that  the 
early  histological  changes  to  be  observed  in  arteries  with  less  elas- 
ticity were  fragmentation  and  alteration  in  the  staining  qualities 
of  the  elastic  fibres. 

It  is  not  an  uncommon  finding  at  autopsy,  that  the  aorta  of  aged 
persons,  with  little  or  no  intimal  sclerosis,  is  thin  and  dilated. 
Such  vessels  owe  their  thinning  to  the  atrophied  media  in  which 
both  muscle  and  elastic  fibres  take  part.  These  arteries  are  less 
elastic  than  those  of  young  adults,  but  the  lumen  is  more  or  less 
uniformly  enlarged.  These  dilatations  do  not  merit  the  term  aneu- 
rysm but  constitute  diffuse  ectases  of  the  aorta. 

Among  the  rarer  forms  of  aneurysm  is  that  type  first  described 
by  Laennec  in  1826  as  "  dissecting  aneurysm."  This  form  con- 
sists of  a  rupture  of  the  inner  surface  of  an  artery,  into  the  media, 
while  the  blood  there  burrows  a  sac  between  the  layers  of  this  tunic, 
and  the  outer  coats  remain  intact.  Some  controversy  had  arisen 
concerning  the  exact  position  which  was  commonly  taken  by  dis- 
secting aneurysms  in  the  arterial  wall.  Pennock  in  1839  gave  an 
excellent  report  of  a  specimen  in  which  he  found  that  the  dissecting 
blood  had  invaded  and  separated  the  layers  of  the  media.  This  is 
now  accepted,  and  it  is  found  that  the  commonest  line  of  separation 
is  between  the  middle  and  outer  thirds  of  this  coat.  The  line  of 
separation  does  not  lie  between  the  adventitia  and  media  as  was 
formerly  supposed. 

Most  of  the  text  books,  Orth,  Ziegler,  Kaufmann  and  others, 
state  that  the  line  of  division  in  dissecting  aneurysms  is  produced 
by  the  inflowing  blood.  This  is  denied  by  some.  It  is  admitted  by 
most,  and  this  is  obtained  from  the  clinical  history,  that  the  direct 
cause  of  the  tear  in  the  inner  coat  of  the  artery  is  brought  on  by 
trauma.  However,  several  cases  have  been  reported  in  which  a 
granulation  tissue  was  found  immediately  about  the  dissecting  aneu- 


Aneurysms  and  Medial  Diseases.  93 

rysm.  In  these  cases  it  was  considered  that  this  inflammatory 
change  in  the  arterial  coat  had  preceded  development  of  the  aneu- 
rysm. It  is  found,  however,  that  some  of  these  cases  had  lived 
some  time  after  the  exciting  trauma,  and  the  possibility  remains 
that  the  inflammatory  change  was  a  secondar}^  development.  Such 
a  case  is  reported  by  Recklinghausen.  Another  case  of  this  kind 
is  reported  by  Babes  and  Mironescu.  They  found,  that  not  only 
was  there  an  inflammatory  infiltration  close  to  the  dissecting  aneu- 
rysm (which  was  of  at  least  two  days  standing),  but  that  the  media 
of  the  aorta  showed  an  unusual  tendency  to  separate  into  two  layers 
in  its  outer  part.  Microscopically,  this  vessel  showed  small  spaces, 
which  the  authors  consider  as  potential  factors  of  dissecting  aneu- 
rysm. This  antecedent  condition  they  describe  as  dissecting 
arteritis. 

Dissecting  aneurysms  are  usually  of  sudden  and  rapid  onset. 
They  occur  most  commonly  between  the  ages  of  fifty-five  and  sixty- 
five — more  occur  after  the  age  of  fifty-five  than  before,  an  age 
when  more  or  less  aortic  medial  sclerosis  is  present.  As  Professor 
Adami  points  out,  the  condition  is  not  developed  in  youth  or  early 
adult  life,  and  there  is  an  etiological  relationship  between  age  and 
incidence.  Further,  Adami  clearly  indicates  that  dissecting  aneu- 
rysm is  not  a  development  from  extensive  atheroma.  The  greater 
majority  of  the  reported  cases  showed  some  nodular  but  smooth 
thickening  of  the  intima,  but  evidence  of  atheromatous  ulceration 
and  calcification  was  wanting.  This  is  an  interesting  observation 
which  illustrates  that  the  atheromatous  processes  in  the  deep  intima 
and  inner  media  are  local  disturbances  which  may  erode  into  the 
vessel  lumen  and  then  exist  as  passive  pathological  processes,  the 
outer  wall  of  the  vessel  being  strong  enough  to  withstand  the  blood 
pressure. 

Although  syphilis  plays  the  important  role  in  the  etiology  of  the 
majority  of  aortic  aneurysms,  it  appears  to  be  little  associated 
with  dissecting  aneurysms.  The  syphilitic  aortitis  is  as  we  have 
repeatedly  said  a  chronic  progressive  inflammation,  which  shows 
degenerative  processes  accompanied  by  the  formation  of  scar  tissue. 
Media  is  mainly  destroyed,  and  it  is  the  media  and  adventitia  which 
develop  the  enormous  interlacing  fibrous  tissue.     These  criss-cross 


94  Arteriosclerosis.    Diseases  of  the  Media. 

bundles  of  fibrous  strands  can  be  stretched  and  lead  to  dilatations, 
but  a  rent  in  the  inner  wall  will  not  burrow  in  this  tangled  fibrous 
tissue.  Erosion  or  rupture  of  the  thinned  walls  of  a  syphilitic 
aneurysm  may  occur  and  cause  a  fatal  hsemorrhage,  but  do  not 
lead  to  dissecting  aneurj^sm. 

In  1896,  Adami  collected  about  two  hundred  cases  of  dissecting 
aneurysms  from  the  literature  and  since  this  time  about  forty  more 
have  been  added.  The  early  reports  of  Peacock,  in  which  eighty 
cases  are  recorded,  form  an  excellent  study  of  the  disease. 

Bostroem  believed  that  dissecting  aneurysm  was  due  to  severe 
strain  and  trauma.  With  Adami  and  others  we  must  agree  that 
severe  strain  has  not  infrequently  been  the  exciting  cause,  but  we 
must  also  recognize  the  presence  of  an  antecedent  diseased  artery. 

Dissecting  aneurysms  follow  the  same  rule  which  we  have  indi- 
cated for  aneurysms  in  general,  ''  there  must  be  a  diseased  media." 
Now  we  have  also  pointed  out  that  those  conditions  in  which 
either  an  acute  mesarteritis  or  a  chronic  productive  mesarteritis  is 
present  lead  to  aneurysmal  dilatations,  a  condition  in  which  the 
walls  are  stretched  but  not  actually  ruptured  by  the  internal  blood 
pressure.  Again  it  is  to  be  noted  that  when  an  acute  inflamma- 
tory mesarteritis  is  further  accompanied  by  sudden  strain,  a  tear 
occurs  in  the  unaffected  intima  which  leads  to  fatal  hemorrhage 
through  the  diseased  media  and  adventltia  (myocotic  aneurysms). 

On  the  other  hand  in  dissecting  aneurysms  we  are  dealing  with 
individuals  over  middle  age,  who,  whether  they  show  a  nodular 
endarteritis  or  not,  have  definite  degenerative  changes  unaccom- 
panied bv  a  productive  sclerosis  in  the  media.  This  form  of  disease 
is  of  the  nature  of  the  true  senile  arteriosclerosis  previously  de- 
scribed. The  media  is  atrophied,  the  muscle  cells  are  small  and 
in  part  lost,  the  elastic  fibres  are  coarse  and  have  lost  much  of  their 
elasticity.  Although  the  A^essel  wall  possesses  senile  degenerative 
changes  true  aneurysms  do  not  develop,  the  tissues  still  being  able 
to  withstand  normal  pressure.  When  however  the  vessel  wall  also 
suffers  a  severe  strain  (lifting  hea\y  weight,  straining  at  stool,  a 
fall),  the  intima  may  be  ruptured  by  knife-like  cuts.  These  intimal 
tears  also  include  and  enter  the  upper  media  so  that  the  blood  gains 
entrance  into  the  middle  of  the  media  where  the  blood  pressure  sep- 


Aneurysms  and  Medial  Diseases.  95 

arates  the  lamella  between  the  middle  and  outer  third.  The  course 
of  least  resistance  is  parallel  to  the  long  axis  of  the  artery,  as  the 
majority  of  muscular  fibres  are  disposed  circularly  while  the  elastic 
fibres  form  a  system  of  perforated  tubes  encircling  the  artery. 
The  fairly  healthy  adventitia  also  prevents  the  escape  of  the  blood 
into  the  surrounding  tissues. 

As  with  all  types  of  arteriosclerosis  the  extent  of  the  disease 
process  varies  in  all  individuals,  so  too  the  severity  of  degenerative 
medial  arteriosclerosis  varies  much  in  individuals  over  fifty  years 
of  age,  and  determines  the  potential  danger  of  dissecting  aneurysms 
when  coupled  with  trauma  or  strain. 

There  is  another  type  of  aneurysm  of  the  peripheral  arteries 
which  forms  a  class  quite  by  itself.  These  are  the  small  saccula- 
tions which  develop  in  association  with  periarteritis  nodosa.  It 
will  be  unnecessary  to  again  review  the  nature  and  history  of  this 
rare  disease,  which  we  have  discussed  in  a  previous  chapter.  The 
points,  however,  which  are  of  particular  interest  at  this  point,  are 
the  development  of  multiple  aneurysms — numerous  in  some  speci- 
mens, rare  in  others.  The  pathological  changes  found  by  the 
various  authors  are  remarkably  constant,  and  the  appearance  is 
characteristic.  The  nodules  develop  on  the  medium-sized  arteries 
of  the  abdomen,  heart  or  parenchymatous  organs  and  are  composed 
either  of  solid  tissue  masses,  aneurysms,  or  organized  thrombi 
within  saccular  dilatations.  In  all  instances  localized  degenerative 
features  are  to  be  found  in  the  media  or  in  the  adventitia  and 
media,  while  an  inflammatory  reaction  is  present  in  the  immediate 
neighborhood.  In  a  few  cases  the  arteries,  although  showing  the 
nodules,  have  had  no  true  aneurysms. 

Whatever  be  the  etiological  factor  or  factors  in  this  disease,  focal 
necrosis  or  degeneration  of  the  arterial  coats  is  an  important 
primary  feature.  This  may  or  may  not  be  accompanied  from  the 
first  by  an  inflammatory  reaction,  and  on  the  presence  or  absence  of 
this  reparative  inflammation  depends  the  development  of  aneurysm. 
In  those  cases  where  the  destruction  of  tissue  is  marked  before 
repair  takes  place,  small  sacculations  develop  in  focal  areas.  In 
others  again  the  degeneration  is  accompanied  by  a  lively  repair 
which  builds  a  mass  of  granulation  tissue  on  the  outer  side  of  the 


96  Arteriosclerosis.    Diseases  of  the  Media. 

media  and  in  the  adventitia,  so  that  the  artery  does  not  yield  under 
its  normal  pressure. 

Although  the  etiology  of  this  disease  is  still  in  doubt,  the  devel- 
opment of  aneurysm  follows  the  same  rule  as  has  been  indicated  for 
other  dilatations  above — namely  a  destruction  of  the  medial  tissues. 

By  some  the  disease  has  been  associated  with  syphilis,  and 
although  Verse  has  found  spirochsetze  in  two  cases  of  gummatous 
periarteritis  he  was  unable  to  find  these  organisms  in  the  nodules  of 
true  periarteritis  nodosa.  It  would  probably  be  well  to  subdivide 
the  cases  of  nodular  periarteritis  into  those  of  syphilitic  origin  and 
those  whose  etiology  to-day  remains  uncertain.  The  lesions  of  the 
latter  class  are  often  quite  acute. 

Still  another  type  of  aneurysm  of  the  large  arteries  has  been 
described  associated  with  acute  infections  and  more  particularly 
with  infective  endocarditis.  Acute  infections  of  the  aorta  are 
remarkably  rare,  but  when  present  have  serious  consequences. 
Ponfick  was  the  first  to  describe  the  acute  vascular  changes  occur- 
ring in  "embolic  aneurysm,"  associated  with  endocarditis.  He 
found  this  condition  at  the  bifurcation  of  an  artery,  and  believed 
that  the  aneurysm  was  the  result  of  the  localized  embolus.  Hoch- 
haus  described  a  case  of  advancing  infection  from  the  aortic  valves 
which  led  to  aneurysm.  The  verrucose  process  extended  into  the 
large  vessels  and  along  the  ductus  arteriosus  to  the  pulmonary  artery. 
Eppinger  described  a  series  of  cases  in  which  aneurysm  of  the 
aorta  had  developed  following  an  acute  infection.  Eppinger 
differed  from  Ponfick's  view  in  that  he  believed  that  these  aneu- 
rysms deyeloped  in  consequence  of  an  acute  septic  inflammation  of 
the  media.  Microorganisms  were  demonstrated  in  the  damaged 
tissue  of  the  artery  and  in  the  thrombotic  mass  when  present.  These 
aortic  lesions  were  spoken  of  as  mycotic  aneurysms.  Schroetter 
recognized  the  same  disease  under  the  name  thromboarteritis  sup- 
purativa. In  England,  Church  and  Langton  and  Bowlby  believed 
that  such  aneurysms  developed  from  localized  emboli  which  caused 
nutritional  changes  in  the  arterial  wall,  in  the  nature  of  an  infarct. 

There  are  certain  characteristics  of  these  unusual  aneurysms 
which  are  constant.  They  occur  most  commonly  in  the  ascending 
limb  of  the  aorta,  are  frequently  multiple  and  show  acute  inflamma- 


Aneurysms  and  Medial  Diseases.  97 

tory  conditions  in  the  media.  From  the  intimal  surface  they  have 
characteristic  linear  or  stellate  knife-like  tears  in  the  intima  which 
lead  either  into  the  tissues  of  the  media  producing  a  dissecting 
aneurysm,  or  perforate  the  entire  wall  with  fatal  hemorrhage. 
Their  onset  or  development  is  usually  sudden. 

Thoma,  who  opposed  Eppinger,  took  an  intermediate  stand 
between  the  mechanical  and  inflammatory  theories  of  these  aneu- 
rysms. He  held  that  he  could  demonstrate  an  abnormal  elasticity 
in  the  media  of  these  vessels,  due  to  atrophy  which  was  the  basal 
feature  he  believed  underlying  all  aneurysms. 

Richter  has  described  seven  such  cases  observed  in  Heller's 
laboratory.  The  lesions  were  in  the  aorta  and  associated  with 
endocarditis.  Theile  also  reported  a  case  with  a  four-cornered 
rupture  in  the  ascending  aorta,  and  associated  with  acute  mitral 
and  aortic  endocarditis.  McCrae  recently  reported  sinother  case 
with  multiple  lesions  in  the  ascending  aorta. 

Mycotic  aneurysm,  therefore,  results  from  a  type  of  acute  mes- 
arteritis,  probably  arising  from  an  infection  entering  the  media  by 
the  nutrient  vessels.  In  several  cases  the  bacteria  have  been  demon- 
strated in  the  lesion. 

In  a  word  we  may  dispense  with  the  discussion  of  aneurysms 
experimentally  produced.  The  earlier  investigators  obtained  in 
their  experiments  of  mechanical  injury  to  the  arteries,  dilatation 
either  diffuse  or  local  at  the  point  of  damage.  Arteries  which  were 
crushed  or  which  had  a  portion  of  the  outer  coats  excised  gave 
way,  sometimes  by  rupture,  at  other  times  in  saccular  ballooning. 
This  is  what  one  would  expect  and  adds  no  new  information  to  the 
observations  made  upon  injured  arteries  in  the  human  subject.  By 
the  method  of  excision  it  is  possible  to  determine  exactly  how  much 
of  the  external  tissues  must  be  lost  before  the  normal  pressure  pro- 
duced a  dilatation.  It  is  to  be  remembered  that  the  strength  of  the 
coats  of  a  vessel  is  dependent  upon  the  artery  affected,  and  upon 
the  health  of  these  tissues.  So,  whereas  in  a  normal  vessel,  the 
intima  and  one  third  of  the  media  can  support  the  blood  pressure 
natural  to  that  vessel,  a  vessel  with  "diseased"  tissues  will  not  be 
able  to  do  so. 

The  later  experiments  with  various  toxins  and  drugs  which  act 


98  Arteriosclerosis.    Diseases  of  the  Media. 

upon  the  media  of  arteries  have  clearly  shown  how  intimately  medial 
scleroses  are  associated  with  aneurysm.  Many  of  these  drugs  pro- 
duce degenerative  lesions  confined  to  the  media  alone  and  many  of 
these  vessels  exhibit  aneurysms,  varying  in  size  dependent  upon  the 
extent  of  the  tissue  involved.  Saccular  and  fusiform  aneurysms 
are  most  readily  produced,  and  B.  Fischer  reports  the  production  of 
a  dissecting  aneurysm  in  the  aorta.  In  no  instance  was  aneurysm 
ever  produced  without  definite  changes  in  the  media,  while  at  the 
same  time  aneurysm  often  occurred  in  the  absence  of  disease  in 
either  the  intima  or  adventitia. 

Experimentally  aneurysms  have  also  been  produced  by  mechan- 
ically and  intermittently  raising  the  blood  pressure.  Such  aneu- 
rysms have  been  explained  as  dilatations  resulting  from  overstrain 
and  fatigue  of  the  elements  of  the  media. 

Process  Underlying  the  Various  Forms  of  Aneurysm. — It  is  not 
our  intention  to  repeat  the  discussion  concerning  the  different  kinds 
of  aneurysm,  but  to  point  out  that  each  type  of  aneurysm  in  the 
accepted  classification  has  its  underlying  cause  which  conforms  with 
one  of  the  types  of  the  diseases  of  the  media,  as  we  have  arranged 
them.  From  this  standpoint  we  are  able  to  more  readily  appreciate 
the  processes  at  work  in  the  production  of  aneurysm,  and  at  the 
same  time  develop  a  classification  which  is  common  to  medial 
scleroses  and  aneurysms  respectively. 

Granted  that  we  are  agreed  in  the  all  importance  of  medial  dis- 
ease for  the  production  of  aneurysm,  we  may  adopt  the  same  sub- 
divisions above  indicated  for  medial  diseases. 

The  main  classes,  (I)  productive  or  inflammatory  lesions  and 
(II)  degenerative  lesions,  may  be  adopted  for  the  classification  of 
aneur}^sms. 

Using  these  basal  divisions  we  find  that  in  Class  I,  there  is  a 
type  of  aneurysm  (mycotic)  associated  with  an  acute  infective  mes- 
arteritis ;  while  another  type,  multiple  nodular  aneurysms,  are  asso- 
ciated with  the  unusual  disease,  periarteritis  nodosa. 

As  we  have  seen  severe  chronic  productive  or  inflammatory  proc- 
esses in  the  media  are  mostly  of  syphilitic  origin  and  give  rise  to 
saccular  aneurysms  of  the  aorta.  That  type  of  chronic  productive 
mesarteritis  which  is   secondary  to   chronic  endarteritis,   Chiari's 


Aneurysms  and  Medial  Diseases.  99 

Type  A,  gives  rise  to  the  sporadic  aneurysms  in  the  peripheral 
arteries,  most  often  seen  in  the  coronary  and  cerebral  arteries,  and 
rarely  if  ever  to  saccular  aneurysm  of  the  aorta. 

Of  the  second  class  of  medial  diseases,  the  degenerative  changes, 
there  are  several  types  which  are  the  forerunners  of  aneurysm. 
Simple  atrophy  of  the  media,  and  particularly  that  of  old  age  leads 
to  slight  and  diffuse  ectases,  more  commonly  obsen^ed  in  the  aorta. 

Senile  arteriosclerosis  of  the  media  of  the  aorta  in  which  fibroses 
are  not  evident,  when  coupled  with  strain  or  trauma  is  the  factor 
of  greatest  importance  in  dissecting  aneurysm. 

]\Iedial  scleroses  of  the  peripheral  arteries,  which  we  have 
referred  to  as  ^loenckeberg's  type,  are  directly  associated  with,  and 
the  precursors  of  the  multiple  pouchings  which  are  found  in  the 
vessels  of  the  extremities  and  less  frequently  in  the  vessels  of  the 
abdomen. 

By  experimental  means  we  have  been  able  by  the  use  of  certain 
drugs  and  also  by  the  intermittent  increase  of  the  blood  pressure  to 
produce  fusiform  aneurysms  and  pouchings  of  the  arterial  coat. 
In  these  instances  the  media  showed  degenerative  changes  like  those 
found  in  the  Moenckeberg  type. 

It  is  seen  therefore  that  the  different  types  and  situations  of 
aneurysms  have  their  reason  in  the  nature  of  the  medial  disease 
which  ■  precedes  them ;  and  that  the  medial  disease  is  in  part 
dependent  upon  the  artery  affected. 


SUMMARY. 

The  media  is  the  mainstay  of  an  artery,  and  upon  its  integrity 
depends  the  resisting  power  against  intravascular  pressure.  It  is 
evident  that  the  media  is  a  very  important,  if  not  the  most  important 
structure  of  an  artery  to  carry  out  its  proper  function,  and  it 
follows  that  the  disease  processes  attacking  the  media,  hold  a  very 
important  place  in  the  general  discussion  of  arteriosclerosis.  The 
very  fact  that  some  type  of  medial  disease  underlies  every  kind  of 
aneurysm,  puts  this  type  of  arterial  lesion  among  the  most  im- 
portant to  command  our  attention. 

We  have  adopted  the  general  term  medial  arteriosclerosis  for  all 
those  conditions  in  the  arteries,  in  which  the  process  in  the  media  is 
responsible  for  the  hardening  of  the  arterial  wall.  We  have  more- 
over also  discussed  under  this  designation  the  acute  stages  of  the 
diseases  which,  when  in  their  process  of  healing,  lead  to  the  true 
clinical  scleroses.  It  is  fallacious  to  attempt  the  discussion  of  any 
sclerosis  without  considering  the  acute  stage  of  the  disease,  if  such 
was  present. 

To  all  types  of  medial  disease  of  the  arteries  the  term  athero- 
sclerosis (Marchand)  is  inapplicable.  The  coining  of  this  term  was 
to  give  a  clearer  word  picture  of  the  combined  atheromatous  and 
sclerotic  processes  in  the  intima.  True  atheroma  does  not  occur  in 
the  media  save  as  an  extension  of  the  process  from  the  intima. 
There  are,  however,  many  sclerotic  processes  in  the  media,  for  the 
whole  of  which  the  designation  of  medial  arteriosclerosis  seems  the 
best.  The  addition  of  new  terms  to  an  old  and  well  recognized  dis- 
ease can  only  lead  to  confusion,  and  until  certain  definite  types  of 
disease  can  be  segregated  from  the  general  one,  it  is  best  to  leave  the 
nomenclature  undisturbed.  There  is  to-day  at  least  one  type  of 
medial  arteriosclerosis  which  merits  special  recognition  and  that  is 
syphilitic  mesarteritis ;  to  this  there  possibly  might  be  added  a 
second,  Moenckeberg's  arteriosclerosis,  a  degenerative  condition  of 
the  media  following  intermittent  arterial  overstrain. 

For  the  ready  comprehension  of  medial  arteriosclerosis  I  believe 

100 


Sumynary.  101 

that  the  subdivisions  as  are  given  above  will  prove  an  aid.  Specific 
names  are  not  suggested  for  any  of  these  classes,  for  the  distinct 
purpose  of  retaining  the  general  class  name  of  medial  arterio- 
sclerosis for  all,  and  naming  the  types  by  their -pathological  char- 
acters. I  have  also  avoided  speaking  of  the  different  types  of 
medial  arteriosclerosis  by  the  names  of  their  etiological  factors,  as 
it  is  impossible  to  distinguish  those  types  in  this  manner.  The 
infectious  and  the  toxic  types  have  under  certain  circumstances 
identical  appearances,  and  these  in  turn  have  some  resemblance  to 
"  work  "  arteriosclerosis.  Hence  it  seems  to  me  that  we  can  do  no 
better  than  to  group  the  varieties  of  medial  arteriosclerosis  accord- 
ing to  their  pathological  processes.  In  our  arrangement  of  these 
diseases  there  are  two  main  classes  of  medial  arteriosclerosis,  (I) 
the  productive  and  (II)  the  degenerative  type.  The  former  can  be 
subdivided  into  three,  the  latter  into  seven  groups  according  to  the 
character  of  the  lesions  (see  page  17). 

In  suggesting  this  classification  of  the  medial  diseases  of  the 
arteries  we  fully  appreciate  the  difficulties  and  the  arguments  which 
may  be  brought  against  it.  Primarily,  we  cannot  deny  the  fre- 
quency with  which  productive  lesions  are  associated  with  degenera- 
tive ones,  but  when  the  given  specimen  is  closely  studied  it  is  possi- 
ble to  determine  the  nature  of  the  primary  and  most  important 
lesion.  Some  types  of  productive  arterial  changes  are  prone  to  be 
followed  by  degenerations,  while  on  the  other  hand  degenerative 
processes  are  often  accompanied  by  or  stimulate  productive  fibroses. 
But  in  classifying  an  arterial  lesion  we  must  consider  not  only  the 
most  apparent  condition  then  present,  but  also  the  process  bringing 
it  about. 

The  principal  factors  leading  to  medial  arterial  disease  are :  ( i ) 
Infections,  (2)  poisons,  (3)  work  and  (4)  old  age  (physiological 
wear  and  tear).  The  effect  of  any  one  of  these  factors  upon 
the  arteries  is  dependent  upon  the  histological  structure  of  that 
artery  and  also  upon  its  function.  The  same  agent  may  give  rise 
to  several  kinds  of  arteriosclerotic  processes,  but  the  presence  of 
arterial  disease  in  one  system  of  vessels  does  not  indicate  disease 
in  another  arterial  system.  Medial  sclerosis  is  often  present  in 
the  absence  of  intimal  arteriosclerosis  in  the  same  vessel. 


102  Arteriosclerosis.    Diseases  of  the  Media. 

In  different  stages  of  its  course,  medial  arteriosclerosis  alters  its 
character,  so  that  at  different  times  it  would  be  differently  classified. 

Aneurysms  are  directly  dependent  upon  the  diseases  of  the  media 
of  arteries,  and  the  nature  of  the  aneurysm  is  determined  by  the 
character  of  the  disease  in  the  media.  The  different  forms  of 
aneurysm  can  be  classified  along  with  the  particular  medial  diseases, 
as  is  indicated  in  the  previous  chapter. 

Syphilis  is  the  most  important  factor  leading  to  chronic  mesar- 
teritis  and  aneurysm  of  the  aorta.  On  the  other  hand,  medial 
weakenings  from  causes  other  than  syphilis  are  more  frequently 
associated  with  aneuiysms  of  the  peripheral  arteries.  Taken  all 
in  all,  the  aneurysms  of  the  peripheral  arteries  are  more  common 
than  aneurysms  of  the  aorta.  In  the  peripheral  system  of  arteries, 
toxins  and  work  are  among  the  important  agents  leading  to  medial 
lesions   resulting  in  aneurysms. 

From  a  clinical  standpoint  the  presence  of  medial  arterio-sclerosis 
is  an  indication  to  reduce  as  far  as  possible  work  and  intoxications. 


.^'ydliography .  103 


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